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Zachary James Reitman

Assistant Professor of Radiation Oncology
Radiation Oncology
30 Duke Medicine Circle, Box 3085, Durham, NC 27710
30 Duke Medicine Circle, Box 3085, Durham, NC 27710

Selected Publications


Determinants of Symptomatic Intracranial Progression After an Initial Stereotactic Radiosurgery Course.

Journal Article Adv Radiat Oncol · June 2024 PURPOSE: Clinical and imaging surveillance of patients with brain metastases is important after stereotactic radiosurgery (SRS) because many will experience intracranial progression (ITCP) requiring multidisciplinary management. The prognostic significance ... Full text Link to item Cite

Dose-Incorporated Deep Ensemble Learning for Improving Brain Metastasis Stereotactic Radiosurgery Outcome Prediction.

Journal Article Int J Radiat Oncol Biol Phys · April 12, 2024 PURPOSE: To develop a novel deep ensemble learning model for accurate prediction of brain metastasis (BM) local control outcomes after stereotactic radiosurgery (SRS). METHODS AND MATERIALS: A total of 114 brain metastases (BMs) from 82 patients were evalu ... Full text Link to item Cite

Long-Term Intracranial Outcomes With Combination Dual Immune-Checkpoint Blockade and Stereotactic Radiosurgery in Patients With Melanoma and Non-Small Cell Lung Cancer Brain Metastases.

Journal Article Int J Radiat Oncol Biol Phys · April 1, 2024 PURPOSE: The intracranial benefit of offering dual immune-checkpoint inhibition (D-ICPI) with ipilimumab and nivolumab to patients with melanoma or non-small cell lung cancer (NSCLC) receiving stereotactic radiosurgery (SRS) for brain metastases (BMs) is u ... Full text Link to item Cite

Coexisting Biopsy-Diagnosed Dementia and Glioblastoma.

Journal Article Brain Sci · January 30, 2024 Both glioblastoma (GBM) and dementia are devastating diseases with limited treatments that are usually not curative. Having clinically diagnosed dementia with an associated biopsy-proven etiology and a coexisting GBM diagnosis is a rare occurrence. The rel ... Full text Link to item Cite

Understanding and therapeutically exploiting cGAS/STING signaling in glioblastoma.

Journal Article J Clin Invest · January 16, 2024 Since the discovery that cGAS/STING recognizes endogenous DNA released from dying cancer cells and induces type I interferon and antitumor T cell responses, efforts to understand and therapeutically target the STING pathway in cancer have ensued. Relative ... Full text Link to item Cite

A road map for the treatment of pediatric diffuse midline glioma.

Journal Article Cancer Cell · January 8, 2024 Recent clinical trials for H3K27-altered diffuse midline gliomas (DMGs) have shown much promise. We present a consensus roadmap and identify three major barriers: (1) refinement of experimental models to include immune and brain-specific components; (2) co ... Full text Link to item Cite

Effects of Ataxia-Telangiectasia Mutated Variants on Radionecrosis and Local Control After Stereotactic Radiation Surgery for Non-Small Cell Lung Cancer Brain Metastases.

Journal Article Adv Radiat Oncol · January 2024 PURPOSE: Genetic variants affecting the radiation response protein ataxia-telangiectasia mutated (ATM) have been associated with increased adverse effects of radiation but also with improved local control after conventional radiation therapy. However, it i ... Full text Link to item Cite

Single-fraction Radiation Treatment Dose Response in a Genetically Engineered Mouse Model of Medulloblastoma.

Journal Article Radiat Res · December 1, 2023 Medulloblastoma is the most common malignant brain tumor of children. Although standard of care radiotherapy for pediatric medulloblastoma (PM) can lead to long-term remission or cure in many patients, it can also cause life-long cognitive impairment and o ... Full text Link to item Cite

Mining cancer genomes for change-of-metabolic-function mutations.

Journal Article Commun Biol · November 10, 2023 Enzymes with novel functions are needed to enable new organic synthesis techniques. Drawing inspiration from gain-of-function cancer mutations that functionally alter proteins and affect cellular metabolism, we developed METIS (Mutated Enzymes from Tumors ... Full text Link to item Cite

Pooled genetic screens to identify vulnerabilities in TERT-promoter-mutant glioblastoma.

Journal Article Oncogene · October 2023 Pooled genetic screens represent a powerful approach to identify vulnerabilities in cancer. Here we used pooled CRISPR/Cas9-based approaches to identify vulnerabilities associated with telomerase reverse transcriptase (TERT) promoter mutations (TPMs) found ... Full text Link to item Cite

Clinical Applications of Immunotherapy for Recurrent Glioblastoma in Adults.

Journal Article Cancers (Basel) · July 31, 2023 Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Despite standard therapies, including resection and chemoradiation, recurrence is virtually inevitable. Current treatment for recurrent glioblastoma (rGBM) is rapidly evolving, ... Full text Link to item Cite

Novel Mechanisms and Future Opportunities for the Management of Radiation Necrosis in Patients Treated for Brain Metastases in the Era of Immunotherapy.

Journal Article Cancers (Basel) · April 24, 2023 Radiation necrosis, also known as treatment-induced necrosis, has emerged as an important adverse effect following stereotactic radiotherapy (SRS) for brain metastases. The improved survival of patients with brain metastases and increased use of combined s ... Full text Link to item Cite

Ganglioglioma deep transcriptomics reveals primitive neuroectoderm neural precursor-like population.

Journal Article Acta Neuropathol Commun · March 25, 2023 Gangliogliomas are brain tumors composed of neuron-like and macroglia-like components that occur in children and young adults. Gangliogliomas are often characterized by a rare population of immature astrocyte-appearing cells expressing CD34, a marker expre ... Full text Link to item Cite

Inducing primary brainstem gliomas in genetically engineered mice using RCAS/TVA retroviruses and Cre/loxP recombination.

Journal Article STAR Protoc · March 17, 2023 Genetically engineered mice are commonly used to model brainstem gliomas in pre-clinical research. One technique for inducing primary tumors in these genetically engineered mice involves delivering viral vectors containing the code for gene-editing protein ... Full text Link to item Cite

Outcomes in Patients with Intact and Resected Brain Metastasis Treated with 5-Fraction Stereotactic Radiosurgery.

Journal Article Adv Radiat Oncol · 2023 PURPOSE: Hypofractionated stereotactic radiosurgery (HF-SRS) with or without surgical resection is potentially a preferred treatment for larger or symptomatic brain metastases (BMs). Herein, we report clinical outcomes and predictive factors following HF-S ... Full text Link to item Cite

Clinical Factors Associated With 30-Day Mortality Among Patients Undergoing Radiation Therapy for Brain Metastases.

Journal Article Adv Radiat Oncol · 2023 PURPOSE: Existing brain metastasis prognostic models do not identify patients at risk of very poor survival after radiation therapy (RT). Identifying patient and disease risk factors for 30-day mortality (30-DM) after RT may help identify patients who woul ... Full text Link to item Cite

Long-term outcomes with reduced-dose whole-brain radiotherapy and a stereotactic radiosurgery boost for primary central nervous system lymphoma.

Journal Article Neurooncol Adv · 2023 BACKGROUND: Primary central nervous system lymphoma (PCNSL) is an aggressive diffuse large B-cell lymphoma. Treatment approaches are historically associated with neurotoxicity, particularly with high-dose whole-brain radiotherapy (WBRT). We hypothesized th ... Full text Link to item Cite

ABL1 and ABL2 promote medulloblastoma leptomeningeal dissemination.

Journal Article Neurooncol Adv · 2023 BACKGROUND: Medulloblastoma is the most common malignant pediatric brain tumor, and leptomeningeal dissemination (LMD) of medulloblastoma both portends a poorer prognosis at diagnosis and is incurable at recurrence. The biological mechanisms underlying LMD ... Full text Link to item Cite

Prognostic Model for Intracranial Progression after Stereotactic Radiosurgery: A Multicenter Validation Study.

Journal Article Cancers (Basel) · October 22, 2022 Stereotactic radiosurgery (SRS) is a standard of care for many patients with brain metastases. To optimize post-SRS surveillance, this study aimed to validate a previously published nomogram predicting post-SRS intracranial progression (IP). We identified ... Full text Link to item Cite

The Effect of Atm Loss on Radiosensitivity of a Primary Mouse Model of Pten-Deleted Brainstem Glioma.

Journal Article Cancers (Basel) · September 17, 2022 Diffuse midline gliomas arise in the brainstem and other midline brain structures and cause a large proportion of childhood brain tumor deaths. Radiation therapy is the most effective treatment option, but these tumors ultimately progress. Inhibition of th ... Full text Link to item Cite

Determinants of Symptomatic Intracranial Progression After an Initial Stereotactic Radiosurgery Course.

Journal Article Adv Radiat Oncol · June 2024 PURPOSE: Clinical and imaging surveillance of patients with brain metastases is important after stereotactic radiosurgery (SRS) because many will experience intracranial progression (ITCP) requiring multidisciplinary management. The prognostic significance ... Full text Link to item Cite

Dose-Incorporated Deep Ensemble Learning for Improving Brain Metastasis Stereotactic Radiosurgery Outcome Prediction.

Journal Article Int J Radiat Oncol Biol Phys · April 12, 2024 PURPOSE: To develop a novel deep ensemble learning model for accurate prediction of brain metastasis (BM) local control outcomes after stereotactic radiosurgery (SRS). METHODS AND MATERIALS: A total of 114 brain metastases (BMs) from 82 patients were evalu ... Full text Link to item Cite

Long-Term Intracranial Outcomes With Combination Dual Immune-Checkpoint Blockade and Stereotactic Radiosurgery in Patients With Melanoma and Non-Small Cell Lung Cancer Brain Metastases.

Journal Article Int J Radiat Oncol Biol Phys · April 1, 2024 PURPOSE: The intracranial benefit of offering dual immune-checkpoint inhibition (D-ICPI) with ipilimumab and nivolumab to patients with melanoma or non-small cell lung cancer (NSCLC) receiving stereotactic radiosurgery (SRS) for brain metastases (BMs) is u ... Full text Link to item Cite

Coexisting Biopsy-Diagnosed Dementia and Glioblastoma.

Journal Article Brain Sci · January 30, 2024 Both glioblastoma (GBM) and dementia are devastating diseases with limited treatments that are usually not curative. Having clinically diagnosed dementia with an associated biopsy-proven etiology and a coexisting GBM diagnosis is a rare occurrence. The rel ... Full text Link to item Cite

Understanding and therapeutically exploiting cGAS/STING signaling in glioblastoma.

Journal Article J Clin Invest · January 16, 2024 Since the discovery that cGAS/STING recognizes endogenous DNA released from dying cancer cells and induces type I interferon and antitumor T cell responses, efforts to understand and therapeutically target the STING pathway in cancer have ensued. Relative ... Full text Link to item Cite

A road map for the treatment of pediatric diffuse midline glioma.

Journal Article Cancer Cell · January 8, 2024 Recent clinical trials for H3K27-altered diffuse midline gliomas (DMGs) have shown much promise. We present a consensus roadmap and identify three major barriers: (1) refinement of experimental models to include immune and brain-specific components; (2) co ... Full text Link to item Cite

Effects of Ataxia-Telangiectasia Mutated Variants on Radionecrosis and Local Control After Stereotactic Radiation Surgery for Non-Small Cell Lung Cancer Brain Metastases.

Journal Article Adv Radiat Oncol · January 2024 PURPOSE: Genetic variants affecting the radiation response protein ataxia-telangiectasia mutated (ATM) have been associated with increased adverse effects of radiation but also with improved local control after conventional radiation therapy. However, it i ... Full text Link to item Cite

Single-fraction Radiation Treatment Dose Response in a Genetically Engineered Mouse Model of Medulloblastoma.

Journal Article Radiat Res · December 1, 2023 Medulloblastoma is the most common malignant brain tumor of children. Although standard of care radiotherapy for pediatric medulloblastoma (PM) can lead to long-term remission or cure in many patients, it can also cause life-long cognitive impairment and o ... Full text Link to item Cite

Mining cancer genomes for change-of-metabolic-function mutations.

Journal Article Commun Biol · November 10, 2023 Enzymes with novel functions are needed to enable new organic synthesis techniques. Drawing inspiration from gain-of-function cancer mutations that functionally alter proteins and affect cellular metabolism, we developed METIS (Mutated Enzymes from Tumors ... Full text Link to item Cite

Pooled genetic screens to identify vulnerabilities in TERT-promoter-mutant glioblastoma.

Journal Article Oncogene · October 2023 Pooled genetic screens represent a powerful approach to identify vulnerabilities in cancer. Here we used pooled CRISPR/Cas9-based approaches to identify vulnerabilities associated with telomerase reverse transcriptase (TERT) promoter mutations (TPMs) found ... Full text Link to item Cite

Clinical Applications of Immunotherapy for Recurrent Glioblastoma in Adults.

Journal Article Cancers (Basel) · July 31, 2023 Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Despite standard therapies, including resection and chemoradiation, recurrence is virtually inevitable. Current treatment for recurrent glioblastoma (rGBM) is rapidly evolving, ... Full text Link to item Cite

Novel Mechanisms and Future Opportunities for the Management of Radiation Necrosis in Patients Treated for Brain Metastases in the Era of Immunotherapy.

Journal Article Cancers (Basel) · April 24, 2023 Radiation necrosis, also known as treatment-induced necrosis, has emerged as an important adverse effect following stereotactic radiotherapy (SRS) for brain metastases. The improved survival of patients with brain metastases and increased use of combined s ... Full text Link to item Cite

Ganglioglioma deep transcriptomics reveals primitive neuroectoderm neural precursor-like population.

Journal Article Acta Neuropathol Commun · March 25, 2023 Gangliogliomas are brain tumors composed of neuron-like and macroglia-like components that occur in children and young adults. Gangliogliomas are often characterized by a rare population of immature astrocyte-appearing cells expressing CD34, a marker expre ... Full text Link to item Cite

Inducing primary brainstem gliomas in genetically engineered mice using RCAS/TVA retroviruses and Cre/loxP recombination.

Journal Article STAR Protoc · March 17, 2023 Genetically engineered mice are commonly used to model brainstem gliomas in pre-clinical research. One technique for inducing primary tumors in these genetically engineered mice involves delivering viral vectors containing the code for gene-editing protein ... Full text Link to item Cite

Outcomes in Patients with Intact and Resected Brain Metastasis Treated with 5-Fraction Stereotactic Radiosurgery.

Journal Article Adv Radiat Oncol · 2023 PURPOSE: Hypofractionated stereotactic radiosurgery (HF-SRS) with or without surgical resection is potentially a preferred treatment for larger or symptomatic brain metastases (BMs). Herein, we report clinical outcomes and predictive factors following HF-S ... Full text Link to item Cite

Clinical Factors Associated With 30-Day Mortality Among Patients Undergoing Radiation Therapy for Brain Metastases.

Journal Article Adv Radiat Oncol · 2023 PURPOSE: Existing brain metastasis prognostic models do not identify patients at risk of very poor survival after radiation therapy (RT). Identifying patient and disease risk factors for 30-day mortality (30-DM) after RT may help identify patients who woul ... Full text Link to item Cite

Long-term outcomes with reduced-dose whole-brain radiotherapy and a stereotactic radiosurgery boost for primary central nervous system lymphoma.

Journal Article Neurooncol Adv · 2023 BACKGROUND: Primary central nervous system lymphoma (PCNSL) is an aggressive diffuse large B-cell lymphoma. Treatment approaches are historically associated with neurotoxicity, particularly with high-dose whole-brain radiotherapy (WBRT). We hypothesized th ... Full text Link to item Cite

ABL1 and ABL2 promote medulloblastoma leptomeningeal dissemination.

Journal Article Neurooncol Adv · 2023 BACKGROUND: Medulloblastoma is the most common malignant pediatric brain tumor, and leptomeningeal dissemination (LMD) of medulloblastoma both portends a poorer prognosis at diagnosis and is incurable at recurrence. The biological mechanisms underlying LMD ... Full text Link to item Cite

Prognostic Model for Intracranial Progression after Stereotactic Radiosurgery: A Multicenter Validation Study.

Journal Article Cancers (Basel) · October 22, 2022 Stereotactic radiosurgery (SRS) is a standard of care for many patients with brain metastases. To optimize post-SRS surveillance, this study aimed to validate a previously published nomogram predicting post-SRS intracranial progression (IP). We identified ... Full text Link to item Cite

The Effect of Atm Loss on Radiosensitivity of a Primary Mouse Model of Pten-Deleted Brainstem Glioma.

Journal Article Cancers (Basel) · September 17, 2022 Diffuse midline gliomas arise in the brainstem and other midline brain structures and cause a large proportion of childhood brain tumor deaths. Radiation therapy is the most effective treatment option, but these tumors ultimately progress. Inhibition of th ... Full text Link to item Cite

Radiosensitizing the Vasculature of Primary Brainstem Gliomas Fails to Improve Tumor Response to Radiation Therapy.

Journal Article Int J Radiat Oncol Biol Phys · March 1, 2022 PURPOSE: Diffuse intrinsic pontine gliomas (DIPGs) arise in the pons and are the leading cause of death from brain tumors in children. DIPGs are routinely treated with radiation therapy, which temporarily improves neurological symptoms but generally fails ... Full text Link to item Cite

PPM1D mutations are oncogenic drivers of de novo diffuse midline glioma formation.

Journal Article Nat Commun · February 1, 2022 The role of PPM1D mutations in de novo gliomagenesis has not been systematically explored. Here we analyze whole genome sequences of 170 pediatric high-grade gliomas and find that truncating mutations in PPM1D that increase the stability of its phosphatase ... Full text Link to item Cite

Targeting the ATM Kinase to Enhance the Efficacy of Radiotherapy and Outcomes for Cancer Patients.

Journal Article Seminars in radiation oncology · January 2022 Targeting the DNA damage response represents a promising approach to improve the efficacy of radiation therapy. One appealing target for this approach is the serine/threonine kinase ataxia telangiectasia mutated (ATM), which is activated by DNA double stra ... Full text Cite

A Modified Nucleoside 6-Thio-2'-Deoxyguanosine Exhibits Antitumor Activity in Gliomas.

Journal Article Clin Cancer Res · December 15, 2021 PURPOSE: To investigate the therapeutic role of a novel telomere-directed inhibitor, 6-thio-2'-deoxyguanosine (THIO) in gliomas both in vitro and in vivo. EXPERIMENTAL DESIGN: A panel of human and mouse glioma cell lines was used to test therapeutic effica ... Full text Link to item Cite

Combining Laser Interstitial Thermal Therapy With SRS Improves Time to Progression for Recurrent SRS-Treated Brain Metastases.

Conference International journal of radiation oncology, biology, physics · November 2021 Purpose/objective(s)Improved survival for patients with brain metastases (BM) has been accompanied by a rise in tumor recurrence after stereotactic radiosurgery (SRS). Laser interstitial thermal therapy (LITT) has evolved as an effective treatment ... Full text Cite

A Dosimetric Study Comparing Two Beam Arrangement Strategies in Fractionated Thoracic Spine Stereotactic Body Radiotherapy (SBRT) Planning.

Conference International journal of radiation oncology, biology, physics · November 2021 Purpose/objective(s)To compare dosimetric results of two beam arrangement strategies and their robustness to setup uncertainties in fractionated thoracic spine Stereotactic Body Radiotherapy (SBRT) MATERIALS/METHODS: Fifteen patients who received ... Full text Cite

A Need for More Molecular Profiling in Brain Metastases.

Journal Article Front Oncol · 2021 As local disease control improves, the public health impact of brain metastases (BrM) continues to grow. Molecular features are frequently different between primary and metastatic tumors as a result of clonal evolution during neoplasm migration, selective ... Full text Link to item Cite

Mitogenic and progenitor gene programmes in single pilocytic astrocytoma cells.

Journal Article Nat Commun · August 19, 2019 Pilocytic astrocytoma (PA), the most common childhood brain tumor, is a low-grade glioma with a single driver BRAF rearrangement. Here, we perform scRNAseq in six PAs using methods that enabled detection of the rearrangement. When compared to higher-grade ... Full text Link to item Cite

Impact of pemetrexed on intracranial disease control and radiation necrosis in patients with brain metastases from non-small cell lung cancer receiving stereotactic radiation.

Journal Article Radiother Oncol · March 2018 BACKGROUND: Pemetrexed is a folate antimetabolite used in the management of advanced adenocarcinoma of the lung. We sought to assess the impact of pemetrexed on intracranial disease control and radiation-related toxicity among patients with adenocarcinoma ... Full text Link to item Cite

Synthesis and evaluation of radiolabeled AGI-5198 analogues as candidate radiotracers for imaging mutant IDH1 expression in tumors.

Journal Article Bioorg Med Chem Lett · February 15, 2018 Mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) are commonly found in gliomas. AGI-5198, a potent and selective inhibitor of the mutant IDH1 enzyme, was radiolabeled with radioiodine and fluorine-18. These radiotracers were evaluated as ... Full text Link to item Cite

New Directions in the Treatment of Glioblastoma.

Journal Article Semin Neurol · February 2018 Glioblastoma (GBM) is the most common primary malignant tumor of the central nervous system. The current standard of care for GBM is maximal resection followed by postoperative radiation with concomitant and adjuvant temozolomide. Despite this multimodalit ... Full text Link to item Cite

Radiolabeled inhibitors as probes for imaging mutant IDH1 expression in gliomas: Synthesis and preliminary evaluation of labeled butyl-phenyl sulfonamide analogs.

Journal Article Eur J Med Chem · August 25, 2016 INTRODUCTION: Malignant gliomas frequently harbor mutations in the isocitrate dehydrogenase 1 (IDH1) gene. Studies suggest that IDH mutation contributes to tumor pathogenesis through mechanisms that are mediated by the neomorphic metabolite of the mutant I ... Full text Open Access Link to item Cite

Detecting somatic mutations in genomic sequences by means of Kolmogorov-Arnold analysis.

Journal Article R Soc Open Sci · August 2015 The Kolmogorov-Arnold stochasticity parameter technique is applied for the first time to the study of cancer genome sequencing, to reveal mutations. Using data generated by next-generation sequencing technologies, we have analysed the exome sequences of br ... Full text Link to item Cite

Genetic dissection of leukemia-associated IDH1 and IDH2 mutants and D-2-hydroxyglutarate in Drosophila.

Journal Article Blood · January 8, 2015 Gain-of-function mutations in nicotinamide adenine dinucleotide phosphate-dependent isocitrate dehydrogenase (IDH)1 and IDH2 frequently arise in human leukemias and other cancers and produce high levels of D-2-hydroxyglutarate (D-2HG). We expressed the R19 ... Full text Link to item Cite

Cancer-associated isocitrate dehydrogenase 1 (IDH1) R132H mutation and d-2-hydroxyglutarate stimulate glutamine metabolism under hypoxia.

Journal Article J Biol Chem · August 22, 2014 Mutations in the cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDH1) occur in several types of cancer, and altered cellular metabolism associated with IDH1 mutations presents unique therapeutic opportunities. By altering IDH1, these mutations targe ... Full text Link to item Cite

Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas.

Journal Article Nat Genet · July 2014 Gliomas arising in the brainstem and thalamus are devastating tumors that are difficult to surgically resect. To determine the genetic and epigenetic landscape of these tumors, we performed exomic sequencing of 14 brainstem gliomas (BSGs) and 12 thalamic g ... Full text Link to item Cite

Tert promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal.

Journal Article Neuro Oncol · July 2014 Malignant cells must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thalassemia/mental retardation syndrome ... Full text Link to item Cite

Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas.

Journal Article Oncotarget · March 30, 2014 Frequent mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) and the promoter of telomerase reverse transcriptase (TERT) represent two significant discoveries in glioma genomics. Understanding the degree to which these two mutations co-occur or o ... Full text Open Access Link to item Cite

The genetic landscape of anaplastic astrocytoma.

Journal Article Oncotarget · March 30, 2014 Anaplastic astrocytoma WHO grade III (A3) is a lethal brain tumor that often occurs in middle aged patients. Clinically, it is challenging to distinguish A3 from glioblastoma multiforme (GBM) WHO grade IV. To reveal the genetic landscape of this tumor type ... Full text Link to item Cite

Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas

Journal Article Nature Genetics · January 1, 2014 Gliomas arising in the brainstem and thalamus are devastating tumors that are difficult to surgically resect. To determine the genetic and epigenetic landscape of these tumors, we performed exomic sequencing of 14 brainstem gliomas (BSGs) and 12 thalamic g ... Full text Cite

Releasing the block: setting differentiation free with mutant IDH inhibitors.

Journal Article Cancer Cell · May 13, 2013 Hotspot mutations in IDH1 and IDH2 cause a differentiation block that can promote tumorigenesis. Two recent papers reported that small molecules targeting mutant IDH1 or mutant IDH2 release this differentiation block and/or impede tumor growth, providing a ... Full text Link to item Cite

TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal.

Journal Article Proc Natl Acad Sci U S A · April 9, 2013 Malignant cells, like all actively growing cells, must maintain their telomeres, but genetic mechanisms responsible for telomere maintenance in tumors have only recently been discovered. In particular, mutations of the telomere binding proteins alpha thala ... Full text Link to item Cite

Exomic sequencing of four rare central nervous system tumor types.

Journal Article Oncotarget · April 2013 A heterogeneous population of uncommon neoplasms of the central nervous system (CNS) cause significant morbidity and mortality. To explore their genetic origins, we sequenced the exomes of 12 pleomorphic xanthoastrocytomas (PXA), 17 non-brainstem pediatric ... Full text Link to item Cite

Disruption of wild-type IDH1 suppresses D-2-hydroxyglutarate production in IDH1-mutated gliomas.

Journal Article Cancer Res · January 15, 2013 Point mutations at Arg132 of the cytoplasmic NADP(+)-dependent isocitrate dehydrogenase 1 (IDH1) occur frequently in gliomas and result in a gain of function to produce the "oncometabolite" D-2-hydroxyglutarate (D-2HG). The mutated IDH1 allele is usually a ... Full text Open Access Link to item Cite

Enzyme redesign guided by cancer-derived IDH1 mutations.

Journal Article Nat Chem Biol · November 2012 Mutations in an enzyme can result in a neomorphic catalytic activity in cancers. We applied cancer-associated mutations from isocitrate dehydrogenases to homologous residues in the active sites of homoisocitrate dehydrogenases to derive enzymes that cataly ... Full text Link to item Cite

Frequent ATRX, CIC, FUBP1 and IDH1 mutations refine the classification of malignant gliomas.

Journal Article Oncotarget · July 2012 Mutations in the critical chromatin modifier ATRX and mutations in CIC and FUBP1, which are potent regulators of cell growth, have been discovered in specific subtypes of gliomas, the most common type of primary malignant brain tumors. However, the frequen ... Full text Open Access Link to item Cite

Relationship Between Time of First Publication and Subsequent Publication Success Among Non-PhD Physician-Scientists.

Journal Article J Grad Med Educ · June 2012 BACKGROUND: Studies have shown that publication of work during medical school and residency is associated with higher numbers of later publications and citations of published research. However, it is unknown whether this association exists for non-PhD phys ... Full text Link to item Cite

Profiling the effects of isocitrate dehydrogenase 1 and 2 mutations on the cellular metabolome.

Journal Article Proc Natl Acad Sci U S A · February 22, 2011 Point mutations of the NADP(+)-dependent isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) occur early in the pathogenesis of gliomas. When mutated, IDH1 and IDH2 gain the ability to produce the metabolite (R)-2-hydroxyglutarate (2HG), but the downstream e ... Full text Link to item Cite

2-hydroxyglutarate production, but not dominant negative function, is conferred by glioma-derived NADP-dependent isocitrate dehydrogenase mutations.

Journal Article PLoS One · February 4, 2011 BACKGROUND: Gliomas frequently contain mutations in the cytoplasmic NADP(+)-dependent isocitrate dehydrogenase (IDH1) or the mitochondrial NADP(+)-dependent isocitrate dehydrogenase (IDH2). Several different amino acid substitutions recur at either IDH1 R1 ... Full text Link to item Cite

IDH1(R132) mutation identified in one human melanoma metastasis, but not correlated with metastases to the brain.

Journal Article Biochem Biophys Res Commun · July 30, 2010 Isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) are enzymes which convert isocitrate to alpha-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP+to NADPH). IDH1/2 were recently identified as mutated in a ... Full text Open Access Link to item Cite

Isocitrate dehydrogenase 1 and 2 mutations in cancer: alterations at a crossroads of cellular metabolism.

Journal Article J Natl Cancer Inst · July 7, 2010 Dysregulation of metabolism is a common phenomenon in cancer cells. The NADP(+)-dependent isocitrate dehydrogenases 1 and 2 (IDH1 and IDH2) function at a crossroads of cellular metabolism in lipid synthesis, cellular defense against oxidative stress, oxida ... Full text Link to item Cite

IDH1 and IDH2: not your typical oncogenes.

Journal Article Cancer Cell · March 16, 2010 Oncogenes usually increase their normal function when activated. However, seemingly oncogenic mutations in IDH1 and IDH2 reduce their native enzyme activity. In this issue of Cancer Cell, Ward et al. pin down a neomorphic enzyme activity as a possible onco ... Full text Link to item Cite

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Journal Article New England Journal of Medicine · May 21, 2009 Full text Cite

Picornavirus genome replication. Identification of the surface of the poliovirus (PV) 3C dimer that interacts with PV 3Dpol during VPg uridylylation and construction of a structural model for the PV 3C2-3Dpol complex.

Journal Article J Biol Chem · January 11, 2008 Picornaviruses have a peptide termed VPg covalently linked to the 5'-end of the genome. Attachment of VPg to the genome occurs in at least two steps. First, Tyr-3 of VPg, or some precursor thereof, is used as a primer by the viral RNA-dependent RNA polymer ... Full text Link to item Cite