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Steven George Rozen

Steven George Rozen

Professor in Biostatistics & Bioinformatics
Biostatistics & Bioinformatics, Division of Integrative Genomics
sr110@duke.edu
2424 Erwin Road, Durham, NC 27710
2424 Erwin Road, Durham, NC 27710

Selected Publications

Distinct genomic subgroups and mutational patterns in undifferentiated/dedifferentiated endometrial carcinoma.

Journal Article BMC Cancer · October 9, 2025 BACKGROUND: Endometrial cancer represents a significant global health challenge, with undifferentiated and dedifferentiated endometrial carcinoma (UDEC) being a particularly aggressive subset. METHODS: We employed whole-exome sequencing (WES) to comprehens ... Full text Link to item Cite

Transcriptomic predictors of prostate cancer recurrence following focal cryotherapy: a pooled analysis of phase II trial and prospective cohort data.

Journal Article J Natl Cancer Cent · October 2025 OBJECTIVE: Focal therapy (FT) is a potential treatment option for limited-volume clinically-significant prostate cancer (csPCa). However, despite rigorous selection, approximately 20% of patients experience early failure. We investigated the association of ... Full text Link to item Cite

Benchmarking 13 tools for mutational signature attribution, including a new and improved algorithm.

Journal Article Brief Bioinform · November 22, 2024 Mutational signatures are characteristic patterns of mutations caused by endogenous mutational processes or by exogenous mutational exposures. There has been little benchmarking of approaches for determining which signatures are present in a sample and est ... Full text Link to item Cite

Molecular profiling reveals novel therapeutic targets and clonal evolution in ovarian clear cell carcinoma.

Journal Article BMC Cancer · November 14, 2024 BACKGROUND: Ovarian clear cell carcinoma (OCCC) has a disproportionately high incidence among women in East Asia. Patients diagnosed with OCCC tend to experience worse clinical outcomes than those with high-grade serous carcinoma (HGSC) at advanced stages. ... Full text Link to item Cite

Oncogene-Driven Non-Small Cell Lung Cancers in Patients with a History of Smoking Lack Smoking-Induced Mutations.

Journal Article Cancer Res · June 14, 2024 UNLABELLED: Non-small cell lung cancers (NSCLC) in nonsmokers are mostly driven by mutations in the oncogenes EGFR, ERBB2, and MET and fusions involving ALK and RET. In addition to occurring in nonsmokers, alterations in these "nonsmoking-related oncogenes ... Full text Link to item Cite

Deep whole-genome analysis of 494 hepatocellular carcinomas.

Journal Article Nature · March 2024 Over half of hepatocellular carcinoma (HCC) cases diagnosed worldwide are in China1-3. However, whole-genome analysis of hepatitis B virus (HBV)-associated HCC in Chinese individuals is limited4-8, with current analyses of HCC mainly from non-HBV-enriched ... Full text Link to item Cite

Patient-reported functional outcomes and oncological control after primary focal cryotherapy for clinically significant prostate cancer: A Phase II mandatory biopsy-monitored study.

Journal Article Prostate · June 2023 INTRODUCTION: We report herein the impact of focal therapy (FT) on multi-domain functional outcomes in a Phase II prospective clinical trial (NCT04138914) in focal cryotherapy for clinically significant prostate cancer (csPCa). METHODS: The primary outcome ... Full text Link to item Cite

mSigHdp: hierarchical Dirichlet process mixture modeling for mutational signature discovery.

Journal Article NAR Genom Bioinform · March 2023 Mutational signatures are characteristic patterns of mutations caused by endogenous or exogenous mutational processes. These signatures can be discovered by analyzing mutations in large sets of samples-usually somatic mutations in tumor samples. Most progr ... Full text Link to item Cite

Uncovering novel mutational signatures by de novo extraction with SigProfilerExtractor.

Journal Article Cell Genom · November 9, 2022 Mutational signature analysis is commonly performed in cancer genomic studies. Here, we present SigProfilerExtractor, an automated tool for de novo extraction of mutational signatures, and benchmark it against another 13 bioinformatics tools by using 34 sc ... Full text Link to item Cite

A genomic-augmented multivariate prognostic model for the survival of natural-killer/T-cell lymphoma patients from an international cohort.

Journal Article Am J Hematol · September 2022 With lowering costs of sequencing and genetic profiling techniques, genetic drivers can now be detected readily in tumors but current prognostic models for Natural-killer/T cell lymphoma (NKTCL) have yet to fully leverage on them for prognosticating patien ... Full text Link to item Cite

Genetic characterization of a missense mutation in the X-linked TAF7L gene identified in an oligozoospermic man†.

Journal Article Biol Reprod · July 25, 2022 Although hundreds of knockout mice show infertility as a major phenotype, the causative genic mutations of male infertility in humans remain rather limited. Here, we report the identification of a missense mutation (D136G) in the X-linked TAF7L gene as a p ... Full text Link to item Cite

Acetyl-CoA metabolism drives epigenome change and contributes to carcinogenesis risk in fatty liver disease.

Journal Article Genome Med · June 23, 2022 BACKGROUND: The incidence of non-alcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is increasing worldwide, but the steps in precancerous hepatocytes which lead to HCC driver mutations are not well understood. Here we provide ... Full text Link to item Cite

Recurrent mutations in topoisomerase IIα cause a previously undescribed mutator phenotype in human cancers.

Journal Article Proc Natl Acad Sci U S A · January 25, 2022 Topoisomerases nick and reseal DNA to relieve torsional stress associated with transcription and replication and to resolve structures such as knots and catenanes. Stabilization of the yeast Top2 cleavage intermediates is mutagenic in yeast, but whether th ... Full text Link to item Cite

Accuracy of mutational signature software on correlated signatures.

Journal Article Sci Rep · January 10, 2022 Mutational signatures are characteristic patterns of mutations generated by exogenous mutagens or by endogenous mutational processes. Mutational signatures are important for research into DNA damage and repair, aging, cancer biology, genetic toxicology, an ... Full text Link to item Cite

Highly recurrent CBS epimutations in gastric cancer CpG island methylator phenotypes and inflammation.

Journal Article Genome Biol · June 1, 2021 BACKGROUND: CIMP (CpG island methylator phenotype) is an epigenetic molecular subtype, observed in multiple malignancies and associated with the epigenetic silencing of tumor suppressors. Currently, for most cancers including gastric cancer (GC), mechanism ... Full text Link to item Cite

The mutational landscape of early- and typical-onset oral tongue squamous cell carcinoma.

Journal Article Cancer · February 15, 2021 BACKGROUND: The incidence of oral tongue squamous cell carcinoma (OTSCC) is increasing among younger birth cohorts. The etiology of early-onset OTSCC (diagnosed before the age of 50 years) and cancer driver genes remain largely unknown. METHODS: The Sequen ... Full text Link to item Cite

Mutational processes in cancer preferentially affect binding of particular transcription factors.

Journal Article Sci Rep · February 8, 2021 Protein binding microarrays provide comprehensive information about the DNA binding specificities of transcription factors (TFs), and can be used to quantitatively predict the effects of DNA sequence variation on TF binding. There has also been substantial ... Full text Open Access Link to item Cite

Enhancer-derived long non-coding RNAs CCAT1 and CCAT2 at rs6983267 has limited predictability for early stage colorectal carcinoma metastasis.

Journal Article Sci Rep · January 11, 2021 Up-regulation of long non-coding RNAs (lncRNAs), colon-cancer associated transcript (CCAT) 1 and 2, was associated with worse prognosis in colorectal cancer (CRC). Nevertheless, their role in predicting metastasis in early-stage CRC is unclear. We measured ... Full text Link to item Cite

Family history assessment significantly enhances delivery of precision medicine in the genomics era.

Journal Article Genome Med · January 7, 2021 BACKGROUND: Family history has traditionally been an essential part of clinical care to assess health risks. However, declining sequencing costs have precipitated a shift towards genomics-first approaches in population screening programs rendering the valu ... Full text Link to item Cite

Utility of Mutational Spectra to Identify Tumor Origin.

Conference ENVIRONMENTAL AND MOLECULAR MUTAGENESIS · 2021 Cite

Author Correction: Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples.

Journal Article Nat Commun · November 30, 2020 Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20128-w. ... Full text Link to item Cite

Multiomic analysis and immunoprofiling reveal distinct subtypes of human angiosarcoma.

Journal Article J Clin Invest · November 2, 2020 Angiosarcomas are rare, clinically aggressive tumors with limited treatment options and a dismal prognosis. We analyzed angiosarcomas from 68 patients, integrating information from multiomic sequencing, NanoString immuno-oncology profiling, and multiplex i ... Full text Link to item Cite

Mutational selection in normal urothelium.

Journal Article Science · October 2, 2020 Full text Link to item Cite

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples.

Journal Article Nat Commun · September 21, 2020 The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis ... Full text Link to item Cite

Sex differences in oncogenic mutational processes.

Journal Article Nat Commun · August 28, 2020 Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations wit ... Full text Link to item Cite

A tumor-associated splice-isoform of MAP2K7 drives dedifferentiation in MBNL1-low cancers via JNK activation.

Journal Article Proc Natl Acad Sci U S A · July 14, 2020 Master splicing regulator MBNL1 shapes large transcriptomic changes that drive cellular differentiation during development. Here we demonstrate that MBNL1 is a suppressor of tumor dedifferentiation. We surveyed MBNL1 expression in matched tumor/normal pair ... Full text Link to item Cite

SRSF1 mediates cytokine-induced impaired imatinib sensitivity in chronic myeloid leukemia.

Journal Article Leukemia · July 2020 Patients with chronic myeloid leukemia (CML) who are treated with tyrosine kinase inhibitors (TKIs) experience significant heterogeneity regarding depth and speed of responses. Factors intrinsic and extrinsic to CML cells contribute to response heterogenei ... Full text Link to item Cite

Integrated paired-end enhancer profiling and whole-genome sequencing reveals recurrent CCNE1 and IGF2 enhancer hijacking in primary gastric adenocarcinoma.

Journal Article Gut · June 2020 OBJECTIVE: Genomic structural variations (SVs) causing rewiring of cis-regulatory elements remain largely unexplored in gastric cancer (GC). To identify SVs affecting enhancer elements in GC (enhancer-based SVs), we integrated epigenomic enhancer profiles ... Full text Link to item Cite

Genomic and epigenomic EBF1 alterations modulate TERT expression in gastric cancer.

Journal Article J Clin Invest · June 1, 2020 Transcriptional reactivation of telomerase catalytic subunit (TERT) is a frequent hallmark of cancer, occurring in 90% of human malignancies. However, specific mechanisms driving TERT reactivation remain obscure for many tumor types and in particular gastr ... Full text Link to item Cite

Characterization of colibactin-associated mutational signature in an Asian oral squamous cell carcinoma and in other mucosal tumor types.

Journal Article Genome Res · June 2020 Mutational signatures can reveal the history of mutagenic processes that cells were exposed to before and during tumorigenesis. We expect that as-yet-undiscovered mutational processes will shed further light on mutagenesis leading to carcinogenesis. With t ... Full text Link to item Cite

A functional network of gastric-cancer-associated splicing events controlled by dysregulated splicing factors.

Journal Article NAR Genom Bioinform · June 2020 Comprehensive understanding of aberrant splicing in gastric cancer is lacking. We RNA-sequenced 19 gastric tumor-normal pairs and identified 118 high-confidence tumor-associated (TA) alternative splicing events (ASEs) based on high-coverage sequencing and ... Full text Link to item Cite

Lack of Targetable FGFR2 Fusions in Endemic Fluke-Associated Cholangiocarcinoma.

Journal Article JCO Glob Oncol · April 2020 PURPOSE: Cholangiocarcinoma (CCA) remains a disease with poor prognosis and limited therapeutic options. Identification of driver genetic alterations may lead to the discovery of more effective targeted therapies. CCAs harboring FGFR2 fusions have recently ... Full text Link to item Cite

Integrative genomic study of Chinese clear cell renal cell carcinoma reveals features associated with thrombus.

Journal Article Nat Commun · February 6, 2020 Clear cell renal cell carcinoma (ccRCC) is a heterogeneous disease with features that vary by ethnicity. A systematic characterization of the genomic landscape of Chinese ccRCC is lacking, and features of ccRCC associated with tumor thrombus (ccRCC-TT) rem ... Full text Link to item Cite

The repertoire of mutational signatures in human cancer.

Journal Article Nature · February 2020 Somatic mutations in cancer genomes are caused by multiple mutational processes, each of which generates a characteristic mutational signature1. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium2 of the International Cancer Genom ... Full text Link to item Cite

Pan-cancer analysis of whole genomes.

Journal Article Nature · February 2020 Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1-3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matchin ... Full text Link to item Cite

Family History Assessment Significantly Enhances Delivery of Precision Medicine in the Genomics Era

Journal Article · January 30, 2020 AbstractBackgroundFamily history has traditionally been an essential part of clinical care to assess health risks. However, declining sequencing costs have precipitated a shift towards gen ... Full text Cite

Toward clinical understanding of aristolochic acid upper-tract urothelial carcinoma.

Journal Article Theranostics · January 2020 A cluster of patients poisoned by herbal medicine in the 1990s revealed that aristolochic acid (AA) causes kidney failure and upper tract urothelial carcinoma (UTUC). Recent research demonstrated that this was not an isolated incident; on the contrary, AA ... Full text Cite

Recurrent mutations in topoisomerase 2a cause a novel mutator phenotype in human cancers

Journal Article · 2020 Topoisomerases are essential for genome stability. Here, we link the p.K743N mutation in topoisomerase TOP2A to a previously undescribed mutator phenotype in human cancers. This phenotype primarily generates a distinctive pattern of duplications of 2 to 4 ... Full text Cite

Ultra-deep Sequencing of Blood and Urine to Test for Exposure to Aristolochic Acids.

Conference ENVIRONMENTAL AND MOLECULAR MUTAGENESIS · 2020 Cite

Implementation of genomics in medical practice to deliver precision medicine for an Asian population

Journal Article Npj Genomic Medicine · December 1, 2019 Whilst the underlying principles of precision medicine are comparable across the globe, genomic references, health practices, costs and discrimination policies differ in Asian settings compared to the reported initiatives involving European-derived populat ... Full text Cite

DNA epigenetic signature predictive of benefit from neoadjuvant chemotherapy in oesophageal adenocarcinoma: results from the MRC OE02 trial.

Journal Article Eur J Cancer · December 2019 BACKGROUND: DNA methylation signatures describing distinct histological subtypes of oesophageal cancer have been reported. We studied DNA methylation in samples from the MRC OE02 phase III trial, which randomised patients with resectable oesophageal cancer ... Full text Link to item Cite

Experimental Delineation of Mutational Signatures Is an Essential Tool in Cancer Epidemiology and Prevention.

Journal Article Chem Res Toxicol · November 18, 2019 Advances in experimental modeling of the mutational signatures of environmental exposures and endogenous mutagenic processes will elucidate the role of mutagenesis in cancer, facilitate carcinogen classification, and enable new molecular cancer epidemiolog ... Full text Link to item Cite

Digital phenotyping by consumer wearables identifies sleep-associated markers of cardiovascular disease risk and biological aging.

Journal Article Commun Biol · October 4, 2019 Sleep is associated with various health outcomes. Despite their growing adoption, the potential for consumer wearables to contribute sleep metrics to sleep-related biomedical research remains largely uncharacterized. Here we analyzed sleep tracking data, a ... Full text Link to item Cite

Non-Canonical Characteristics of Mutational Signatures Identified By Experimental Modelling.

Conference ENVIRONMENTAL AND MOLECULAR MUTAGENESIS · September 1, 2019 Link to item Cite

SigProfilerMatrixGenerator: a tool for visualizing and exploring patterns of small mutational events.

Journal Article BMC Genomics · August 30, 2019 BACKGROUND: Cancer genomes are peppered with somatic mutations imprinted by different mutational processes. The mutational pattern of a cancer genome can be used to identify and understand the etiology of the underlying mutational processes. A plethora of ... Full text Link to item Cite

Genomic and Transcriptomic Profiling of Combined Hepatocellular and Intrahepatic Cholangiocarcinoma Reveals Distinct Molecular Subtypes.

Journal Article Cancer Cell · June 10, 2019 We performed genomic and transcriptomic sequencing of 133 combined hepatocellular and intrahepatic cholangiocarcinoma (cHCC-ICC) cases, including separate, combined, and mixed subtypes. Integrative comparison of cHCC-ICC with hepatocellular carcinoma and i ... Full text Link to item Cite

Experimental and pan-cancer genome analyses reveal widespread contribution of acrylamide exposure to carcinogenesis in humans.

Journal Article Genome Res · April 2019 Humans are frequently exposed to acrylamide, a probable human carcinogen found in commonplace sources such as most heated starchy foods or tobacco smoke. Prior evidence has shown that acrylamide causes cancer in rodents, yet epidemiological studies conduct ... Full text Open Access Link to item Cite

Population genomics in South East Asia captures unexpectedly high carrier frequency for treatable inherited disorders.

Journal Article Genet Med · January 2019 PURPOSE: Genomic studies have demonstrated the necessity of ethnicity-specific population data to ascertain variant pathogenicity for disease diagnosis and treatment. This study examined the carrier prevalence of treatable inherited disorders (TIDs), where ... Full text Link to item Cite

SigProfilerMatrixGenerator: a tool for visualizing and exploring patterns of small mutational events

Journal Article · 2019 ABSTRACTBackground Cancer genomes are peppered with somatic mutations imprinted by different mutational processes. The mutational pattern of a cancer genome can be used to identify and understand the etiology of the underlying mutational ... Full text Cite

Digital phenotyping by consumer wearables identifies sleep-associated markers of cardiovascular disease risk and biological aging.

Journal Article Commun Biol · 2019 Sleep is associated with various health outcomes. Despite their growing adoption, the potential for consumer wearables to contribute sleep metrics to sleep-related biomedical research remains largely uncharacterized. Here we analyzed sleep tracking data, a ... Full text Link to item Cite

Correction: Population genomics in South East Asia captures unexpectedly high carrier frequency for treatable inherited disorders.

Journal Article Genet Med · December 2018 At the time of publication the author Jyn Ling Kuan did not have a master's degree; this has now been amended to BSc. This has now been corrected in the PDF and HTML versions of the article. ... Full text Link to item Cite

Genome-wide mutational signature of glycidamide observed in human cancers using PCAWG data

Conference ENVIRONMENTAL AND MOLECULAR MUTAGENESIS · September 1, 2018 Link to item Cite

In-depth characterization of the cisplatin mutational signature in human cell lines and in esophageal and liver tumors.

Journal Article Genome Res · May 2018 Cisplatin reacts with DNA and thereby likely generates a characteristic pattern of somatic mutations, called a mutational signature. Despite widespread use of cisplatin in cancer treatment and its role in contributing to secondary malignancies, its mutatio ... Full text Link to item Cite

Functional genomics identifies specific vulnerabilities in PTEN-deficient breast cancer.

Journal Article Breast Cancer Res · March 22, 2018 BACKGROUND: Phosphatase and tensin homolog (PTEN) is one of the most frequently inactivated tumor suppressors in breast cancer. While PTEN itself is not considered a druggable target, PTEN synthetic-sick or synthetic-lethal (PTEN-SSL) genes are potential d ... Full text Link to item Cite

Amenable epigenetic traits of dental pulp stem cells underlie high capability of xeno-free episomal reprogramming.

Journal Article Stem Cell Res Ther · March 20, 2018 BACKGROUND: While a shift towards non-viral and animal component-free methods of generating induced pluripotent stem (iPS) cells is preferred for safer clinical applications, there is still a shortage of reliable cell sources and protocols for efficient re ... Full text Link to item Cite

Beyond fitness tracking: The use of consumer-grade wearable data from normal volunteers in cardiovascular and lipidomics research.

Journal Article PLoS Biol · February 2018 The use of consumer-grade wearables for purposes beyond fitness tracking has not been comprehensively explored. We generated and analyzed multidimensional data from 233 normal volunteers, integrating wearable data, lifestyle questionnaires, cardiac imaging ... Full text Link to item Cite

Genomic and Epigenomic Profiling of High-Risk Intestinal Metaplasia Reveals Molecular Determinants of Progression to Gastric Cancer.

Journal Article Cancer Cell · January 8, 2018 Intestinal metaplasia (IM) is a pre-malignant condition of the gastric mucosa associated with increased gastric cancer (GC) risk. We performed (epi)genomic profiling of 138 IMs from 148 cancer-free patients, recruited through a 10-year prospective study. C ... Full text Link to item Cite

HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis.

Journal Article Nat Commun · January 8, 2018 The repression of telomerase activity during cellular differentiation promotes replicative aging and functions as a physiological barrier for tumorigenesis in long-lived mammals, including humans. However, the underlying mechanisms remain largely unclear. ... Full text Link to item Cite

<i>VHL</i> Deficiency Drives Enhancer Activation of Oncogenes in Clear Cell Renal Cell Carcinoma.

Journal Article Cancer discovery · November 2017 Protein-coding mutations in clear cell renal cell carcinoma (ccRCC) have been extensively characterized, frequently involving inactivation of the von Hippel-Lindau (VHL) tumor suppressor. Roles for noncoding cis-regulatory aberrations in ccRC ... Full text Cite

The draft genome of tropical fruit durian (Durio zibethinus).

Journal Article Nat Genet · November 2017 Durian (Durio zibethinus) is a Southeast Asian tropical plant known for its hefty, spine-covered fruit and sulfury and onion-like odor. Here we present a draft genome assembly of D. zibethinus, representing the third plant genus in the Malvales order and f ... Full text Link to item Cite

Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia.

Journal Article Sci Transl Med · October 18, 2017 Many traditional pharmacopeias include Aristolochia and related plants, which contain nephrotoxins and mutagens in the form of aristolochic acids and similar compounds (collectively, AA). AA is implicated in multiple cancer types, sometimes with very high ... Full text Link to item Cite

Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma.

Journal Article Cancer Discov · October 2017 Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analyzed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and D ... Full text Link to item Cite

A formalin-fixed paraffin-embedded (FFPE)-based prognostic signature to predict metastasis in clinically low risk stage I/II microsatellite stable colorectal cancer.

Journal Article Cancer Lett · September 10, 2017 Approximately 20% early-stage (I/II) colorectal cancer (CRC) patients develop metastases despite curative surgery. We aim to develop a formalin-fixed and paraffin-embedded (FFPE)-based predictor of metastases in early-stage, clinically-defined low risk, mi ... Full text Link to item Cite

Genome-scale mutational signatures of aflatoxin in cells, mice, and human tumors.

Journal Article Genome Res · September 2017 Aflatoxin B1 (AFB1) is a mutagen and IARC (International Agency for Research on Cancer) Group 1 carcinogen that causes hepatocellular carcinoma (HCC). Here, we present the first whole-genome data on the mutational signatures of AFB1 exposure from a total o ... Full text Link to item Cite

Epigenomic Promoter Alterations Amplify Gene Isoform and Immunogenic Diversity in Gastric Adenocarcinoma.

Journal Article Cancer Discov · June 2017 Promoter elements play important roles in isoform and cell type-specific expression. We surveyed the epigenomic promoter landscape of gastric adenocarcinoma, analyzing 110 chromatin profiles (H3K4me3, H3K4me1, H3K27ac) of primary gastric cancers, gastric c ... Full text Link to item Cite

Nucleus-Translocated ACSS2 Promotes Gene Transcription for Lysosomal Biogenesis and Autophagy.

Journal Article Mol Cell · June 1, 2017 Overcoming metabolic stress is a critical step in tumor growth. Acetyl coenzyme A (acetyl-CoA) generated from glucose and acetate uptake is important for histone acetylation and gene expression. However, how acetyl-CoA is produced under nutritional stress ... Full text Link to item Cite

Wnt proteins synergize to activate β-catenin signaling.

Journal Article J Cell Sci · May 1, 2017 Wnt ligands are involved in diverse signaling pathways that are active during development, maintenance of tissue homeostasis and in various disease states. While signaling regulated by individual Wnts has been extensively studied, Wnts are rarely expressed ... Full text Link to item Cite

Loss of tumor suppressor KDM6A amplifies PRC2-regulated transcriptional repression in bladder cancer and can be targeted through inhibition of EZH2.

Journal Article Sci Transl Med · February 22, 2017 Trithorax-like group complex containing KDM6A acts antagonistically to Polycomb-repressive complex 2 (PRC2) containing EZH2 in maintaining the dynamics of the repression and activation of gene expression through H3K27 methylation. In urothelial bladder car ... Full text Link to item Cite

Multiregion ultra-deep sequencing reveals early intermixing and variable levels of intratumoral heterogeneity in colorectal cancer.

Journal Article Mol Oncol · February 2017 Intratumor heterogeneity (ITH) contributes to cancer progression and chemoresistance. We sought to comprehensively describe ITH of somatic mutations, copy number, and transcriptomic alterations involving clinically and biologically relevant gene pathways i ... Full text Link to item Cite

Individualised multiplexed circulating tumour DNA assays for monitoring of tumour presence in patients after colorectal cancer surgery.

Journal Article Sci Rep · January 19, 2017 Circulating tumour DNA (ctDNA) has the potential to be a specific biomarker for the monitoring of tumours in patients with colorectal cancer (CRC). Here, our aim was to develop a personalised surveillance strategy to monitor the clinical course of CRC afte ... Full text Link to item Cite

Reduced penetrance in a large Caucasian pedigree with Stickler syndrome.

Journal Article Ophthalmic Genet · 2017 BACKGROUND: In a four-generation Caucasian family variably diagnosed with autosomal dominant (AD) Stickler or Wagner disease, commercial gene screening failed to identify a mutation in COL2A1 or VCAN. We utilized linkage mapping and exome sequencing to ide ... Full text Link to item Cite

Molecular genetics of renal cell carcinoma

Chapter · January 1, 2017 In the last decade, from the early large-scale multigene profiling using traditional Sanger sequencing to the more recent next-generation whole-exome and whole-genome sequencing, the genomic landscapes of renal cell carcinoma (RCC), consisting mainly of cl ... Full text Cite

SETD2 histone modifier loss in aggressive GI stromal tumours.

Journal Article Gut · December 2016 BACKGROUND: GI stromal tumours (GISTs) are clinically heterogenous exhibiting varying degrees of disease aggressiveness in individual patients. OBJECTIVES: We sought to identify genetic alterations associated with high-risk GIST, explore their molecular co ... Full text Link to item Cite

Distinct Responses of Stem Cells to Telomere Uncapping-A Potential Strategy to Improve the Safety of Cell Therapy.

Journal Article Stem Cells · October 2016 In most human somatic cells, the lack of telomerase activity results in progressive telomere shortening during each cell division. Eventually, DNA damage responses triggered by critically short telomeres induce an irreversible cell cycle arrest termed repl ... Full text Link to item Cite

ADAR-Mediated RNA Editing Predicts Progression and Prognosis of Gastric Cancer.

Journal Article Gastroenterology · October 2016 BACKGROUD & AIMS: Gastric cancer (GC) is the third leading cause of global cancer mortality. Adenosine-to-inosine RNA editing is a recently described novel epigenetic mechanism involving sequence alterations at the RNA but not DNA level, primarily mediated ... Full text Link to item Cite

Transcription-associated mutation of lasR in Pseudomonas aeruginosa.

Journal Article DNA Repair (Amst) · October 2016 Pseudomonas aeruginosa is an opportunistic pathogen which infects cystic fibrosis and cancer patients with compromised immune systems. LasR is a master regulator which controls the virulence of P. aeruginosa in response to bacterial cell-density and host s ... Full text Link to item Cite

Global re-wiring of p53 transcription regulation by the hepatitis B virus X protein.

Journal Article Mol Oncol · October 2016 BACKGROUND: The tumour suppressor p53 is a central player in transcription regulation and cell fate determination. By interacting with p53 and altering its sequence-specific binding to the response elements, the hepatitis B virus X protein (HBx) was report ... Full text Link to item Cite

Epigenomic profiling of primary gastric adenocarcinoma reveals super-enhancer heterogeneity.

Journal Article Nat Commun · September 28, 2016 Regulatory enhancer elements in solid tumours remain poorly characterized. Here we apply micro-scale chromatin profiling to survey the distal enhancer landscape of primary gastric adenocarcinoma (GC), a leading cause of global cancer mortality. Integrating ... Full text Link to item Cite

Angiopoietin receptor TEK mutations underlie primary congenital glaucoma with variable expressivity.

Journal Article J Clin Invest · July 1, 2016 Primary congenital glaucoma (PCG) is a devastating eye disease and an important cause of childhood blindness worldwide. In PCG, defects in the anterior chamber aqueous humor outflow structures of the eye result in elevated intraocular pressure (IOP); howev ... Full text Open Access Link to item Cite

JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma.

Journal Article Leukemia · June 2016 Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to i ... Full text Link to item Cite

Abundant copy-number loss of CYCLOPS and STOP genes in gastric adenocarcinoma.

Journal Article Gastric Cancer · April 2016 BACKGROUND: Gastric cancer, a leading cause of cancer death worldwide, has been little studied compared with other cancers that impose similar health burdens. Our goal is to assess genomic copy-number loss and the possible functional consequences and thera ... Full text Link to item Cite

NOTUM is a potential pharmacodynamic biomarker of Wnt pathway inhibition.

Journal Article Oncotarget · March 15, 2016 Activation of Wnt signaling due to Wnt overexpression or mutations of Wnt pathway components is associated with various cancers. Blocking Wnt secretion by inhibiting PORCN enzymatic activity has shown efficacy in a subset of cancers with elevated Wnt signa ... Full text Link to item Cite

MiRNA-128 regulates the proliferation and neurogenesis of neural precursors by targeting PCM1 in the developing cortex.

Journal Article Elife · February 17, 2016 During the development, tight regulation of the expansion of neural progenitor cells (NPCs) and their differentiation into neurons is crucial for normal cortical formation and function. In this study, we demonstrate that microRNA (miR)-128 regulates the pr ... Full text Link to item Cite

Differentially Expressed miRNAs in Hepatocellular Carcinoma Target Genes in the Genetic Information Processing and Metabolism Pathways.

Journal Article Sci Rep · January 28, 2016 To date, studies of the roles of microRNAs (miRNAs) in hepatocellular carcinoma (HCC) have either focused on specific individual miRNAs and a small number of suspected targets or simply reported a list of differentially expressed miRNAs based on expression ... Full text Link to item Cite

Exome sequencing reveals recurrent REV3L mutations in cisplatin-resistant squamous cell carcinoma of head and neck.

Journal Article Sci Rep · January 21, 2016 Dacomitinib, an irreversible pan-HER inhibitor, had shown modest clinical activity in squamous cell carcinoma of head and neck (SCCHN) patients. Therefore, validated predictive biomarkers are required to identify patients most likely to benefit from this t ... Full text Link to item Cite

NanoString expression profiling identifies candidate biomarkers of RAD001 response in metastatic gastric cancer.

Journal Article ESMO Open · 2016 BACKGROUND: Gene expression profiling has contributed greatly to cancer research. However, expression-driven biomarker discovery in metastatic gastric cancer (mGC) remains unclear. A gene expression profile predicting RAD001 response in refractory GC was e ... Full text Link to item Cite

Inherited breast cancer predisposition in Asians: multigene panel testing outcomes from Singapore.

Journal Article NPJ Genom Med · 2016 Genetic testing for germline mutations in breast cancer predisposition genes can potentially identify individuals at a high risk of developing breast and/or ovarian cancer. There is a paucity of such mutational information for Asians. Panel testing of 25 c ... Full text Link to item Cite

Whole-exome sequencing of breast cancer, malignant peripheral nerve sheath tumor and neurofibroma from a patient with neurofibromatosis type 1.

Journal Article Cancer Med · December 2015 Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by the development of multiple neurofibromas, cafe-au-lait spots, and Lisch nodules. Individuals with NF1 are at increased risk of developing various tumors, such as malignant peripheral ne ... Full text Link to item Cite

Genomic landscapes of breast fibroepithelial tumors.

Journal Article Nat Genet · November 2015 Breast fibroepithelial tumors comprise a heterogeneous spectrum of pathological entities, from benign fibroadenomas to malignant phyllodes tumors. Although MED12 mutations have been frequently found in fibroadenomas and phyllodes tumors, the landscapes of ... Full text Link to item Cite

Mutational landscapes of tongue carcinoma reveal recurrent mutations in genes of therapeutic and prognostic relevance.

Journal Article Genome Med · September 23, 2015 BACKGROUND: Carcinoma of the oral tongue (OTSCC) is the most common malignancy of the oral cavity, characterized by frequent recurrence and poor survival. The last three decades has witnessed a change in the OTSCC epidemiological profile, with increasing i ... Full text Link to item Cite

TEX11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse.

Journal Article EMBO Mol Med · September 2015 Genome-wide recombination is essential for genome stability, evolution, and speciation. Mouse Tex11, an X-linked meiosis-specific gene, promotes meiotic recombination and chromosomal synapsis. Here, we report that TEX11 is mutated in infertile men with non ... Full text Link to item Cite

MSIseq: Software for Assessing Microsatellite Instability from Catalogs of Somatic Mutations.

Journal Article Sci Rep · August 26, 2015 Microsatellite instability (MSI) is a form of hypermutation that occurs in some tumors due to defects in cellular DNA mismatch repair. MSI is characterized by frequent somatic mutations (i.e., cancer-specific mutations) that change the length of simple rep ... Full text Link to item Cite

Exome-wide Sequencing Shows Low Mutation Rates and Identifies Novel Mutated Genes in Seminomas.

Journal Article Eur Urol · July 2015 BACKGROUND: Testicular germ cell tumors are the most common cancer diagnosed in young men, and seminomas are the most common type of these cancers. There have been no exome-wide examinations of genes mutated in seminomas or of overall rates of nonsilent so ... Full text Link to item Cite

Regulatory crosstalk between lineage-survival oncogenes KLF5, GATA4 and GATA6 cooperatively promotes gastric cancer development.

Journal Article Gut · May 2015 OBJECTIVE: Gastric cancer (GC) is a deadly malignancy for which new therapeutic strategies are needed. Three transcription factors, KLF5, GATA4 and GATA6, have been previously reported to exhibit genomic amplification in GC. We sought to validate these fin ... Full text Link to item Cite

The uric acid transporter SLC2A9 is a direct target gene of the tumor suppressor p53 contributing to antioxidant defense.

Journal Article Oncogene · April 2, 2015 Only humans and higher primates have high uric acid blood levels. Although high uric acid causes gout, it has been linked with human longevity because of its hypothetical antioxidant function. Recent studies reveal that p53 has significant roles in cellula ... Full text Link to item Cite

Pathogenesis of cholangiocarcinoma: From genetics to signalling pathways.

Journal Article Best Pract Res Clin Gastroenterol · April 2015 Cholangiocarcinoma (CCA) is a malignant tumour of bile duct epithelial cells with dismal prognosis and rising incidence. Chronic inflammation resulting from liver fluke infection, hepatitis and other inflammatory bowel diseases is a major contributing fact ... Full text Link to item Cite

Integrative analysis of head and neck cancer identifies two biologically distinct HPV and three non-HPV subtypes.

Journal Article Clin Cancer Res · February 15, 2015 PURPOSE: Current classification of head and neck squamous cell carcinomas (HNSCC) based on anatomic site and stage fails to capture biologic heterogeneity or adequately inform treatment. EXPERIMENTAL DESIGN: Here, we use gene expression-based consensus clu ... Full text Link to item Cite

High-depth sequencing of over 750 genes supports linear progression of primary tumors and metastases in most patients with liver-limited metastatic colorectal cancer.

Journal Article Genome Biol · February 12, 2015 BACKGROUND: Colorectal cancer with metastases limited to the liver (liver-limited mCRC) is a distinct clinical subset characterized by possible cure with surgery. We performed high-depth sequencing of over 750 cancer-associated genes and copy number profil ... Full text Link to item Cite

Whole-exome sequencing studies of parathyroid carcinomas reveal novel PRUNE2 mutations, distinctive mutational spectra related to APOBEC-catalyzed DNA mutagenesis and mutational enrichment in kinases associated with cell migration and invasion.

Journal Article J Clin Endocrinol Metab · February 2015 CONTEXT: Cell division cycle 73 (CDC73), encoding the protein parafibromin, is the most prevalent mutated gene in familial and sporadic parathyroid carcinoma (PC). OBJECTIVE: To identify additional genetic abnormalities in PCs. DESIGN: Whole-exome sequenci ... Full text Link to item Cite

Mutation signatures implicate aristolochic acid in bladder cancer development.

Journal Article Genome Med · 2015 BACKGROUND: Aristolochic acid (AA) is a natural compound found in many plants of the Aristolochia genus, and these plants are widely used in traditional medicines for numerous conditions and for weight loss. Previous work has connected AA-mutagenesis to up ... Full text Link to item Cite

Mutation signatures implicate aristolochic acid in bladder cancer development

Journal Article Genome Medicine · 2015 © 2015 Poon et al.; licensee BioMed Central.Background: Aristolochic acid (AA) is a natural compound found in many plants of the Aristolochia genus, and these plants are widely used in traditional medicines for numerous conditions and for weight loss. Prev ... Full text Cite

Sequencing the mouse Y chromosome reveals convergent gene acquisition and amplification on both sex chromosomes.

Journal Article Cell · November 6, 2014 We sequenced the MSY (male-specific region of the Y chromosome) of the C57BL/6J strain of the laboratory mouse Mus musculus. In contrast to theories that Y chromosomes are heterochromatic and gene poor, the mouse MSY is 99.9% euchromatic and contains about ... Full text Link to item Cite

Abstract 5168: Gastric adenocarcinomas show pervasive loss of heterozygosity and enrichment for “STOP” genes in regions of hemizygous deletion

Conference Cancer Research · October 1, 2014 AbstractPurpose: Gastric cancer, the second leading cause of cancer death worldwide, has been little studied compared with other cancers that impose similar burdens on public health. Our goal is to assess lo ... Full text Cite

Abstract 4270: The use of mutational signatures in identifying carcinogen exposure

Conference Cancer Research · October 1, 2014 AbstractAristolochic acid (AA), a natural product of Aristolochia plants found in herbal remedies and health supplements, is a Group 1 carcinogen that can cause nephrotoxicity and upper urinary tract urothel ... Full text Cite

The NF1 gene revisited - from bench to bedside.

Journal Article Oncotarget · August 15, 2014 Neurofibromatosis type 1 (NF1) is a relatively common tumour predisposition syndrome related to germline aberrations of NF1, a tumour suppressor gene. The gene product neurofibromin is a negative regulator of the Ras cellular proliferation pathway, and als ... Full text Link to item Cite

Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma.

Journal Article Nat Genet · August 2014 Fibroadenomas are the most common breast tumors in women under 30 (refs. 1,2). Exome sequencing of eight fibroadenomas with matching whole-blood samples revealed recurrent somatic mutations solely in MED12, which encodes a Mediator complex subunit. Targete ... Full text Link to item Cite

Nanoscale chromatin profiling of gastric adenocarcinoma reveals cancer-associated cryptic promoters and somatically acquired regulatory elements.

Journal Article Nat Commun · July 10, 2014 Chromatin alterations are fundamental hallmarks of cancer. To study chromatin alterations in primary gastric adenocarcinomas, we perform nanoscale chromatin immunoprecipitation sequencing of multiple histone modifications in five gastric cancers and matche ... Full text Link to item Cite

Lipidomics identifies a requirement for peroxisomal function during influenza virus replication.

Journal Article J Lipid Res · July 2014 Influenza virus acquires a host-derived lipid envelope during budding, yet a convergent view on the role of host lipid metabolism during infection is lacking. Using a mass spectrometry-based lipidomics approach, we provide a systems-scale perspective on me ... Full text Link to item Cite

Evaluation and optimisation of indel detection workflows for ion torrent sequencing of the BRCA1 and BRCA2 genes.

Journal Article BMC Genomics · June 24, 2014 BACKGROUND: The Ion Torrent PGM is a popular benchtop sequencer that shows promise in replacing conventional Sanger sequencing as the gold standard for mutation detection. Despite the PGM's reported high accuracy in calling single nucleotide variations, it ... Full text Link to item Cite

Mammalian Y chromosomes retain widely expressed dosage-sensitive regulators.

Journal Article Nature · April 24, 2014 The human X and Y chromosomes evolved from an ordinary pair of autosomes, but millions of years ago genetic decay ravaged the Y chromosome, and only three per cent of its ancestral genes survived. We reconstructed the evolution of the Y chromosome across e ... Full text Link to item Cite

Mutation signatures of carcinogen exposure: genome-wide detection and new opportunities for cancer prevention.

Journal Article Genome Med · 2014 Exposure to environmental mutagens is an important cause of human cancer, and measures to reduce mutagenic and carcinogenic exposures have been highly successful at controlling cancer. Until recently, it has been possible to connect the chemical characteri ... Full text Link to item Cite

Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel.

Journal Article PLoS One · 2014 Developmental delay and/or intellectual disability (DD/ID) affects 1-3% of all children. At least half of these are thought to have a genetic etiology. Recent studies have shown that massively parallel sequencing (MPS) using a targeted gene panel is partic ... Full text Link to item Cite

Regionally-specified second trimester fetal neural stem cells reveals differential neurogenic programming.

Journal Article PLoS One · 2014 Neural stem/progenitor cells (NSC) have the potential for treatment of a wide range of neurological diseases such as Parkinson Disease and multiple sclerosis. Currently, NSC have been isolated only from hippocampus and subventricular zone (SVZ) of the adul ... Full text Link to item Cite

Exome sequencing identifies distinct mutational patterns in liver fluke-related and non-infection-related bile duct cancers.

Journal Article Nat Genet · December 2013 The impact of different carcinogenic exposures on the specific patterns of somatic mutation in human tumors remains unclear. To address this issue, we profiled 209 cholangiocarcinomas (CCAs) from Asia and Europe, including 108 cases caused by infection wit ... Full text Link to item Cite

Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil.

Journal Article Gastroenterology · September 2013 BACKGROUND & AIMS: Almost all gastric cancers are adenocarcinomas, which have considerable heterogeneity among patients. We sought to identify subtypes of gastric adenocarcinomas with particular biological properties and responses to chemotherapy and targe ... Full text Link to item Cite

Extensive diversity in circadian regulation of plasma lipids and evidence for different circadian metabolic phenotypes in humans.

Journal Article Proc Natl Acad Sci U S A · August 27, 2013 The circadian system regulates daily rhythms in lipid metabolism and adipose tissue function. Although disruption of circadian clock function is associated with negative cardiometabolic end points, very little is known about interindividual variation in ci ... Full text Link to item Cite

Genome-wide mutational signatures of aristolochic acid and its application as a screening tool.

Journal Article Sci Transl Med · August 7, 2013 Aristolochic acid (AA), a natural product of Aristolochia plants found in herbal remedies and health supplements, is a group 1 carcinogen that can cause nephrotoxicity and upper urinary tract urothelial cell carcinoma (UTUC). Whole-genome and exome analysi ... Full text Link to item Cite

Mutations in SCO2 are associated with autosomal-dominant high-grade myopia.

Journal Article Am J Hum Genet · May 2, 2013 Myopia, or near-sightedness, is an ocular refractive error of unfocused image quality in front of the retinal plane. Individuals with high-grade myopia (dioptric power greater than -6.00) are predisposed to ocular morbidities such as glaucoma, retinal deta ... Full text Link to item Cite

Abstract 1200: Molecular subtypes of gastric cancer show systematic differences in response to PI3K inhibitors and fluorouracil.

Conference Cancer Research · April 15, 2013 AbstractBackground & Aims: Gastric cancer is the second leading cause of cancer death worldwide, killing &gt;730,000 people every year. Almost all gastric cancers are adenocarcinomas, which exhibit c ... Full text Cite

Alterations in metabolic pathways and networks in Alzheimer's disease.

Journal Article Transl Psychiatry · April 9, 2013 The pathogenic mechanisms of Alzheimer's disease (AD) remain largely unknown and clinical trials have not demonstrated significant benefit. Biochemical characterization of AD and its prodromal phase may provide new diagnostic and therapeutic insights. We u ... Full text Link to item Cite

Whole exome sequencing identifies a mutation for a novel form of corneal intraepithelial dyskeratosis.

Journal Article J Med Genet · April 2013 BACKGROUND: Corneal intraepithelial dyskeratosis is an extremely rare condition. The classical form, affecting Native American Haliwa-Saponi tribe members, is called hereditary benign intraepithelial dyskeratosis (HBID). Herein, we present a new form of co ... Full text Link to item Cite

CYP1B1, MYOC, and LTBP2 mutations in primary congenital glaucoma patients in the United States.

Journal Article Am J Ophthalmol · March 2013 PURPOSE: To screen primary congenital glaucoma patients in the United States for sequence variants within the CYP1B1, LTBP2, and MYOC genes using Sanger and whole exome sequencing. DESIGN: Retrospective case-control study. METHODS: Fifty-seven primary cong ... Full text Link to item Cite

mTORC1 inhibition restricts inflammation-associated gastrointestinal tumorigenesis in mice.

Journal Article J Clin Invest · February 2013 Gastrointestinal cancers are frequently associated with chronic inflammation and excessive secretion of IL-6 family cytokines, which promote tumorigenesis through persistent activation of the GP130/JAK/STAT3 pathway. Although tumor progression can be preve ... Full text Link to item Cite

Host cell transcriptome profile during wild-type and attenuated dengue virus infection.

Journal Article PLoS Negl Trop Dis · 2013 Dengue viruses 1-4 (DENV1-4) rely heavily on the host cell machinery to complete their life cycle, while at the same time evade the host response that could restrict their replication efficiency. These requirements may account for much of the broad gene-le ... Full text Link to item Cite

Whole-genome reconstruction and mutational signatures in gastric cancer.

Journal Article Genome Biol · December 13, 2012 BACKGROUND: Gastric cancer is the second highest cause of global cancer mortality. To explore the complete repertoire of somatic alterations in gastric cancer, we combined massively parallel short read and DNA paired-end tag sequencing to present the first ... Full text Link to item Cite

AZFc deletions and spermatogenic failure: a population-based survey of 20,000 Y chromosomes.

Journal Article Am J Hum Genet · November 2, 2012 Deletions involving the Y chromosome's AZFc region are the most common known genetic cause of severe spermatogenic failure (SSF). Six recurrent interstitial deletions affecting the region have been reported, but their population genetics are largely unexpl ... Full text Link to item Cite

Methylation subtypes and large-scale epigenetic alterations in gastric cancer.

Journal Article Sci Transl Med · October 17, 2012 Epigenetic alterations are fundamental hallmarks of cancer genomes. We surveyed the landscape of DNA methylation alterations in gastric cancer by analyzing genome-wide CG dinucleotide (CpG) methylation profiles of 240 gastric cancers (203 tumors and 37 cel ... Full text Link to item Cite

Primer3--new capabilities and interfaces.

Journal Article Nucleic Acids Res · August 2012 Polymerase chain reaction (PCR) is a basic molecular biology technique with a multiplicity of uses, including deoxyribonucleic acid cloning and sequencing, functional analysis of genes, diagnosis of diseases, genotyping and discovery of genetic variants. R ... Full text Link to item Cite

TP53 genomic status regulates sensitivity of gastric cancer cells to the histone methylation inhibitor 3-deazaneplanocin A (DZNep).

Journal Article Clin Cancer Res · August 1, 2012 PURPOSE: DZNep (3-deazaneplanocin A) depletes EZH2, a critical component of polycomb repressive complex 2 (PRC2), which is frequently deregulated in cancer. Despite exhibiting promising anticancer activity, the specific genetic determinants underlying DZNe ... Full text Link to item Cite

Janus kinase 3-activating mutations identified in natural killer/T-cell lymphoma.

Journal Article Cancer Discov · July 2012 UNLABELLED: The molecular pathogenesis of natural killer/T-cell lymphoma (NKTCL) is not well understood. We conducted whole-exome sequencing and identified Janus kinase 3 (JAK3) somatic-activating mutations (A572V and A573V) in 2 of 4 patients with NKTCLs. ... Full text Link to item Cite

Primer-BLAST: a tool to design target-specific primers for polymerase chain reaction.

Journal Article BMC Bioinformatics · June 18, 2012 BACKGROUND: Choosing appropriate primers is probably the single most important factor affecting the polymerase chain reaction (PCR). Specific amplification of the intended target requires that primers do not have matches to other targets in certain orienta ... Full text Link to item Cite

Exome sequencing of liver fluke-associated cholangiocarcinoma.

Journal Article Nat Genet · May 6, 2012 Opisthorchis viverrini-related cholangiocarcinoma (CCA), a fatal bile duct cancer, is a major public health concern in areas endemic for this parasite. We report here whole-exome sequencing of eight O. viverrini-related tumors and matched normal tissue. We ... Full text Link to item Cite

A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets.

Journal Article Gut · May 2012 OBJECTIVE: Gastric cancer is a major gastrointestinal malignancy for which targeted therapies are emerging as treatment options. This study sought to identify the most prevalent molecular targets in gastric cancer and to elucidate systematic patterns of ex ... Full text Link to item Cite

Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes.

Journal Article Nat Genet · May 2012 Gastric cancer is a major cause of global cancer mortality. We surveyed the spectrum of somatic alterations in gastric cancer by sequencing the exomes of 15 gastric adenocarcinomas and their matched normal DNAs. Frequently mutated genes in the adenocarcino ... Full text Link to item Cite

Differential pulmonary transcriptomic profiles in murine lungs infected with low and highly virulent influenza H3N2 viruses reveal dysregulation of TREM1 signaling, cytokines, and chemokines.

Journal Article Funct Integr Genomics · March 2012 Investigating the relationships between critical influenza viral mutations contributing to increased virulence and host expression factors will shed light on the process of severe pathogenesis from the systems biology perspective. We previously generated a ... Full text Link to item Cite

Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes.

Journal Article Nature · February 22, 2012 The human X and Y chromosomes evolved from an ordinary pair of autosomes during the past 200-300 million years. The human MSY (male-specific region of Y chromosome) retains only three percent of the ancestral autosomes' genes owing to genetic decay. This e ... Full text Link to item Cite

Genomics and genetics of human and primate y chromosomes.

Journal Article Annu Rev Genomics Hum Genet · 2012 In mammals, the Y chromosome plays the pivotal role in male sex determination and is essential for normal sperm production. Yet only three Y chromosomes have been completely sequenced to date--those of human, chimpanzee, and rhesus macaque. While Y chromos ... Full text Link to item Cite

Improving indel detection specificity of the Ion Torrent PGM benchtop sequencer.

Journal Article PLoS One · 2012 The emergence of benchtop sequencers has made clinical genetic testing using next-generation sequencing more feasible. Ion Torrent's PGM™ is one such benchtop sequencer that shows clinical promise in detecting single nucleotide variations (SNVs) and microi ... Full text Link to item Cite

First somatic mutation of E2F1 in a critical DNA binding residue discovered in well-differentiated papillary mesothelioma of the peritoneum.

Journal Article Genome Biol · September 28, 2011 BACKGROUND: Well differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare variant of epithelial mesothelioma of low malignancy potential, usually found in women with no history of asbestos exposure. In this study, we perform the first exom ... Full text Link to item Cite

Intrinsic subtypes of gastric cancer, based on gene expression pattern, predict survival and respond differently to chemotherapy.

Journal Article Gastroenterology · August 2011 BACKGROUND & AIMS: Gastric cancer (GC) is a heterogeneous disease comprising multiple subtypes that have distinct biological properties and effects in patients. We sought to identify new, intrinsic subtypes of GC by gene expression analysis of a large pane ... Full text Link to item Cite

Defending male fertility.

Journal Article Sci Transl Med · July 20, 2011 An estimated 10 to 15% of couples suffer from infertility, and many treatment decisions rely on trial and error. In this issue of Science Translational Medicine, Tollner and colleagues provide strong evidence from a human genetics study that a common varia ... Full text Link to item Cite

Metabolomic changes in autopsy-confirmed Alzheimer's disease.

Journal Article Alzheimers Dement · May 2011 BACKGROUND: Metabolomics, the global science of biochemistry, provides powerful tools to map perturbations in the metabolic network and enables simultaneous quantification of several metabolites to identify metabolic perturbances that might provide insight ... Full text Link to item Cite

Assessing matched normal and tumor pairs in next-generation sequencing studies.

Journal Article PLoS One · March 18, 2011 Next generation sequencing technology has revolutionized the study of cancers. Through matched normal-tumor pairs, it is now possible to identify genome-wide germline and somatic mutations. The generation and analysis of the data requires rigorous quality ... Full text Link to item Cite

Metabolomics in early Alzheimer's disease: identification of altered plasma sphingolipidome using shotgun lipidomics.

Journal Article PLoS One · 2011 BACKGROUND: The development of plasma biomarkers could facilitate early detection, risk assessment and therapeutic monitoring in Alzheimer's disease (AD). Alterations in ceramides and sphingomyelins have been postulated to play a role in amyloidogensis and ... Full text Link to item Cite

Genetic and structural variation in the gastric cancer kinome revealed through targeted deep sequencing.

Journal Article Cancer Res · January 1, 2011 Genetic alterations in kinases have been linked to multiple human pathologies. To explore the landscape of kinase genetic variation in gastric cancer (GC), we used targeted, paired-end deep sequencing to analyze 532 protein and phosphoinositide kinases in ... Full text Link to item Cite

Altered interactions of tryptophan metabolites in first-episode neuroleptic-naive patients with schizophrenia.

Journal Article Mol Psychiatry · September 2010 Schizophrenia is characterized by complex and dynamically interacting perturbations in multiple neurochemical systems. In the past, evidence for these alterations has been collected piecemeal, limiting our understanding of the interactions among relevant b ... Full text Link to item Cite

Convergent evolution of chicken Z and human X chromosomes by expansion and gene acquisition.

Journal Article Nature · July 29, 2010 In birds, as in mammals, one pair of chromosomes differs between the sexes. In birds, males are ZZ and females ZW. In mammals, males are XY and females XX. Like the mammalian XY pair, the avian ZW pair is believed to have evolved from autosomes, with most ... Full text Link to item Cite

Genome-scale technologies foster advances in neurological and behavioral research

Journal Article Current Psychiatry Reviews · May 1, 2010 Abstract: Neurological and behavioral disorders are often difficult to study: In many cases they are the culmination of years of subtle biological processes, and the nervous system is inherently complex. Thus, researchers have been eager to exploit new, ge ... Full text Cite

Chimpanzee and human Y chromosomes are remarkably divergent in structure and gene content.

Journal Article Nature · January 28, 2010 The human Y chromosome began to evolve from an autosome hundreds of millions of years ago, acquiring a sex-determining function and undergoing a series of inversions that suppressed crossing over with the X chromosome. Little is known about the recent evol ... Full text Link to item Cite

Remarkably little variation in proteins encoded by the Y chromosome's single-copy genes, implying effective purifying selection.

Journal Article Am J Hum Genet · December 2009 Y-linked single-nucleotide polymorphisms (SNPs) have served as powerful tools for reconstructing the worldwide genealogy of human Y chromosomes and for illuminating patrilineal relationships among modern human populations. However, there has been no system ... Full text Link to item Cite

Opioid use affects antioxidant activity and purine metabolism: preliminary results.

Journal Article Hum Psychopharmacol · December 2009 OBJECTIVE: More must be learned about metabolic and biochemical alterations that contribute to the development and expression of drug dependence. Experimental opioid administration influences mechanisms and indices of oxidative stress, such as antioxidant ... Full text Link to item Cite

Y chromosome gr/gr deletions are a risk factor for low semen quality.

Journal Article Hum Reprod · October 2009 BACKGROUND: Subfertility affects one in eight couples. In up to 50% of cases, the male partner has low semen quality. Four Y chromosome deletions, i.e. Azoospermia factor a (AZFa), P5/proximal-P1 (AZFb), P5/distal-P1 and AZFc deletions, are established cau ... Full text Link to item Cite

Alterations in tryptophan and purine metabolism in cocaine addiction: a metabolomic study.

Journal Article Psychopharmacology (Berl) · October 2009 BACKGROUND: Mapping metabolic "signatures" can provide new insights into addictive mechanisms and potentially identify biomarkers and therapeutic targets. OBJECTIVE: We examined the differences in metabolites related to the tyrosine, tryptophan, purine, an ... Full text Link to item Cite

High mutation rates have driven extensive structural polymorphism among human Y chromosomes.

Journal Article Nat Genet · April 2006 Although much structural polymorphism in the human genome has been catalogued, the kinetics of underlying change remain largely unexplored. Because human Y chromosomes are clonally inherited, it has been possible to capture their detailed relationships in ... Full text Link to item Cite

Conservation of Y-linked genes during human evolution revealed by comparative sequencing in chimpanzee.

Journal Article Nature · September 1, 2005 The human Y chromosome, transmitted clonally through males, contains far fewer genes than the sexually recombining autosome from which it evolved. The enormity of this evolutionary decline has led to predictions that the Y chromosome will be completely ber ... Full text Link to item Cite

Metabolomic analysis and signatures in motor neuron disease.

Journal Article Metabolomics · 2005 Motor neuron diseases (MND) are a heterogeneous group of disorders that includes amyotrophic lateral sclerosis (ALS) and result in death of motor neurons. These diseases may produce characteristic perturbations of the metabolome, the collection of small-mo ... Full text Link to item Cite

A family of human Y chromosomes has dispersed throughout northern Eurasia despite a 1.8-Mb deletion in the azoospermia factor c region.

Journal Article Genomics · June 2004 The human Y chromosome is replete with amplicons-very large, nearly identical repeats-which render it susceptible to interstitial deletions that often cause spermatogenic failure. Here we describe a recurrent, 1.8-Mb deletion that removes half of the azoos ... Full text Link to item Cite

Polymorphism for a 1.6-Mb deletion of the human Y chromosome persists through balance between recurrent mutation and haploid selection.

Journal Article Nat Genet · November 2003 Many human Y-chromosomal deletions are thought to severely impair reproductive fitness, which precludes their transmission to the next generation and thus ensures their rarity in the population. Here we report a 1.6-Mb deletion that persists over generatio ... Full text Link to item Cite

Abundant gene conversion between arms of palindromes in human and ape Y chromosomes.

Journal Article Nature · June 19, 2003 Eight palindromes comprise one-quarter of the euchromatic DNA of the male-specific region of the human Y chromosome, the MSY. They contain many testis-specific genes and typically exhibit 99.97% intra-palindromic (arm-to-arm) sequence identity. This high d ... Full text Link to item Cite

The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes.

Journal Article Nature · June 19, 2003 The male-specific region of the Y chromosome, the MSY, differentiates the sexes and comprises 95% of the chromosome's length. Here, we report that the MSY is a mosaic of heterochromatic sequences and three classes of euchromatic sequences: X-transposed, X- ... Full text Link to item Cite

Recombination between palindromes P5 and P1 on the human Y chromosome causes massive deletions and spermatogenic failure.

Journal Article Am J Hum Genet · October 2002 It is widely believed that at least three nonoverlapping regions of the human Y chromosome-AZFa, AZFb, and AZFc ("azoospermia factors" a, b, and c)-are essential for normal spermatogenesis. These intervals are defined by interstitial Y-chromosome deletions ... Full text Link to item Cite

The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men.

Journal Article Nat Genet · November 2001 Deletions of the AZFc (azoospermia factor c) region of the Y chromosome are the most common known cause of spermatogenic failure. We determined the complete nucleotide sequence of AZFc by identifying and distinguishing between near-identical amplicons (mas ... Full text Link to item Cite

A physical map of the human Y chromosome.

Journal Article Nature · February 15, 2001 The non-recombining region of the human Y chromosome (NRY), which comprises 95% of the chromosome, does not undergo sexual recombination and is present only in males. An understanding of its biological functions has begun to emerge from DNA studies of indi ... Full text Link to item Cite

A simple procedure for the analysis of single nucleotide polymorphisms facilitates map-based cloning in Arabidopsis.

Journal Article Plant Physiol · December 2000 We developed a modified allele-specific PCR procedure for assaying single nucleotide polymorphisms (SNPs) and used the procedure (called SNAP for single-nucleotide amplified polymorphisms) to generate 62 Arabidopsis mapping markers. SNAP primers contain a ... Full text Link to item Cite

Deletion of azoospermia factor a (AZFa) region of human Y chromosome caused by recombination between HERV15 proviruses.

Journal Article Hum Mol Genet · September 22, 2000 Deletion of any of three regions of the human Y chromosome results in spermatogenic failure and infertility. We previously sequenced one of these regions, azoospermia factor a (AZFa) and found that it spanned approximately 800 kb. By sequence-tagged site ( ... Full text Link to item Cite

A high-density integrated genetic linkage and radiation hybrid map of the laboratory rat.

Journal Article Genome Res · June 1999 The laboratory rat (Rattus norvegicus) is a key animal model for biomedical research. However, the genetic infrastructure required for connecting phenotype and genotype in the rat is currently incomplete. Here, we report the construction and integration of ... Link to item Cite

New techniques for DNA sequence classification.

Journal Article J Comput Biol · 1999 DNA sequence classification is the activity of determining whether or not an unlabeled sequence S belongs to an existing class C. This paper proposes two new techniques for DNA sequence classification. The first technique works by comparing the unlabeled s ... Full text Link to item Cite

A physical map of 30,000 human genes.

Journal Article Science · October 23, 1998 A map of 30,181 human gene-based markers was assembled and integrated with the current genetic map by radiation hybrid mapping. The new gene map contains nearly twice as many genes as the previous release, includes most genes that encode proteins of known ... Full text Link to item Cite

Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome.

Journal Article Science · May 15, 1998 Single-nucleotide polymorphisms (SNPs) are the most frequent type of variation in the human genome, and they provide powerful tools for a variety of medical genetic studies. In a large-scale survey for SNPs, 2.3 megabases of human genomic DNA was examined ... Full text Link to item Cite

A map of 75 human ribosomal protein genes.

Journal Article Genome Res · May 1998 We mapped 75 genes that collectively encode >90% of the proteins found in human ribosomes. Because localization of ribosomal protein genes (rp genes) is complicated by the existence of processed pseudogenes, multiple strategies were devised to identify PCR ... Full text Link to item Cite

The LabBase system for data management in large scale biology research laboratories.

Journal Article Bioinformatics · 1998 MOTIVATION: The development of laboratory information management systems (LIMSs) for large scale biology research projects can be a challenging problem. Many such projects generate complex datasets via complex procedures that undergo continuous refinement. ... Full text Link to item Cite

The LabFlow system for workflow management in large scale biology research laboratories.

Journal Article Proc Int Conf Intell Syst Mol Biol · 1998 LabFlow is a workflow management system designed for large scale biology research laboratories. It provides a workflow model in which objects flow from task to task under programmatic control. The model supports parallelism, meaning that an object can flow ... Link to item Cite

LabFlow-l: A database benchmark for high-throughput workflow management

Journal Article Lecture Notes in Computer Science Including Subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics · December 1, 1996 Workflow management is a ubiquitous task faced by many organizations, and entails the coordination of various activities. This coordination is increasingly carried out by software systems called workflow management systems (WFMS). An important component of ... Cite

The DAZ gene cluster on the human Y chromosome arose from an autosomal gene that was transposed, repeatedly amplified and pruned.

Journal Article Nat Genet · November 1996 It is widely believed that most or all Y-chromosomal genes were once shared with the X chromosome. The DAZ gene is a candidate for the human Y-chromosomal Azoospermia Factor (AZF). We report multiple copies of DAZ (> 99% identical in DNA sequence) clustere ... Full text Link to item Cite

Genome maps 7. The human transcript map. Wall chart.

Journal Article Science · October 25, 1996 Link to item Cite

Genome maps .7. The human transcript map

Journal Article SCIENCE · October 25, 1996 Link to item Cite

Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene

Journal Article Human Reproduction · January 1, 1996 We have detected deletions of portions of the Y chromosome long arm in 12 of 89 men with azoospermia (no spermatozoa in their semen). No Y deletions were detected in their male relatives or in 90 other fertile males. The 12 deletions overlap, defining a re ... Full text Cite

An STS-based map of the human genome.

Journal Article Science · December 22, 1995 A physical map has been constructed of the human genome containing 15,086 sequence-tagged sites (STSs), with an average spacing of 199 kilobases. The project involved assembly of a radiation hybrid map of the human genome containing 6193 loci and incorpora ... Full text Link to item Cite

Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene.

Journal Article Nat Genet · August 1995 We have detected deletions of portions of the Y chromosome long arm in 12 of 89 men with azoospermia (no sperm in semen). No Y deletions were detected in their male relatives or in 90 other fertile males. The 12 deletions overlap, defining a region likely ... Full text Link to item Cite

LabBase: Managing Lab Data in a Large-Scale Genome-Mapping Project

Journal Article IEEE Engineering in Medicine and Biology Magazine · January 1, 1995 Full text Cite

Splicing UNIX into a genome mapping laboratory

Conference USENIX Summer 1994 Technical Conference · January 1, 1994 © 1994 USENIX Association. All rights reserved. The Whitehead Institute/MIT Center for Genome Research is responsible for a number of large genome mapping efforts, the scale of which create problems of data and workflow management that dictate reliance on ... Cite

Splicing UNIX into a genome mapping laboratory

Conference USENIX Summer 1994 Technical Conference · January 1, 1994 © 1994 USENIX Association. All rights reserved. The Whitehead Institute/MIT Center for Genome Research is responsible for a number of large genome mapping efforts, the scale of which create problems of data and workflow management that dictate reliance on ... Cite

Splicing UNIX into a genome mapping laboratory

Conference Usenix Summer 1994 Technical Conference · January 1, 1994 The Whitehead Institute/MIT Center for Genome Research is responsible for a number of large genome mapping efforts, the scale of which create problems of data and workflow management that dictate reliance on computer support. Two years ago, when we started ... Cite

Using a Relational System on Wall Street: The Good, the Bad, the Ugly, and the Ideal

Journal Article Communications of the ACM · January 8, 1989 Developers of a Wall Street financial application were able to exploit a relational DBMS to advantage for some data management tasks 1989. For others, the relational system was not helpful (the bad), or could be pressed into service only by means of major ... Full text Cite