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Cross-species DNA copy number analyses identifies multiple 1q21-q23 subtype-specific driver genes for breast cancer.

Publication ,  Journal Article
Silva, GO; He, X; Parker, JS; Gatza, ML; Carey, LA; Hou, JP; Moulder, SL; Marcom, PK; Ma, J; Rosen, JM; Perou, CM
Published in: Breast Cancer Res Treat
July 2015

A large number of DNA copy number alterations (CNAs) exist in human breast cancers, and thus characterizing the most frequent CNAs is key to advancing therapeutics because it is likely that these regions contain breast tumor 'drivers' (i.e., cancer causal genes). This study aims to characterize the genomic landscape of breast cancer CNAs and identify potential subtype-specific drivers using a large set of human breast tumors and genetically engineered mouse (GEM) mammary tumors. Using a novel method called SWITCHplus, we identified subtype-specific DNA CNAs occurring at a 15% or greater frequency, which excluded many well-known breast cancer-related drivers such as amplification of ERBB2, and deletions of TP53 and RB1. A comparison of CNAs between mouse and human breast tumors identified regions with shared subtype-specific CNAs. Additional criteria that included gene expression-to-copy number correlation, a DawnRank network analysis, and RNA interference functional studies highlighted candidate driver genes that fulfilled these multiple criteria. Numerous regions of shared CNAs were observed between human breast tumors and GEM mammary tumor models that shared similar gene expression features. Specifically, we identified chromosome 1q21-23 as a Basal-like subtype-enriched region with multiple potential driver genes including PI4KB, SHC1, and NCSTN. This step-wise computational approach based on a cross-species comparison is applicable to any tumor type for which sufficient human and model system DNA copy number data exist, and in this instance, highlights that a single region of amplification may in fact harbor multiple driver genes.

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Published In

Breast Cancer Res Treat

DOI

EISSN

1573-7217

Publication Date

July 2015

Volume

152

Issue

2

Start / End Page

347 / 356

Location

Netherlands

Related Subject Headings

  • Species Specificity
  • Signal Transduction
  • Receptors, Notch
  • Oncology & Carcinogenesis
  • Oncogenes
  • Neoplasms, Basal Cell
  • Mice
  • Humans
  • Gene Regulatory Networks
  • Gene Dosage
 

Citation

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Silva, G. O., He, X., Parker, J. S., Gatza, M. L., Carey, L. A., Hou, J. P., … Perou, C. M. (2015). Cross-species DNA copy number analyses identifies multiple 1q21-q23 subtype-specific driver genes for breast cancer. Breast Cancer Res Treat, 152(2), 347–356. https://doi.org/10.1007/s10549-015-3476-2
Silva, Grace O., Xiaping He, Joel S. Parker, Michael L. Gatza, Lisa A. Carey, Jack P. Hou, Stacy L. Moulder, et al. “Cross-species DNA copy number analyses identifies multiple 1q21-q23 subtype-specific driver genes for breast cancer.Breast Cancer Res Treat 152, no. 2 (July 2015): 347–56. https://doi.org/10.1007/s10549-015-3476-2.
Silva GO, He X, Parker JS, Gatza ML, Carey LA, Hou JP, et al. Cross-species DNA copy number analyses identifies multiple 1q21-q23 subtype-specific driver genes for breast cancer. Breast Cancer Res Treat. 2015 Jul;152(2):347–56.
Silva, Grace O., et al. “Cross-species DNA copy number analyses identifies multiple 1q21-q23 subtype-specific driver genes for breast cancer.Breast Cancer Res Treat, vol. 152, no. 2, July 2015, pp. 347–56. Pubmed, doi:10.1007/s10549-015-3476-2.
Silva GO, He X, Parker JS, Gatza ML, Carey LA, Hou JP, Moulder SL, Marcom PK, Ma J, Rosen JM, Perou CM. Cross-species DNA copy number analyses identifies multiple 1q21-q23 subtype-specific driver genes for breast cancer. Breast Cancer Res Treat. 2015 Jul;152(2):347–356.
Journal cover image

Published In

Breast Cancer Res Treat

DOI

EISSN

1573-7217

Publication Date

July 2015

Volume

152

Issue

2

Start / End Page

347 / 356

Location

Netherlands

Related Subject Headings

  • Species Specificity
  • Signal Transduction
  • Receptors, Notch
  • Oncology & Carcinogenesis
  • Oncogenes
  • Neoplasms, Basal Cell
  • Mice
  • Humans
  • Gene Regulatory Networks
  • Gene Dosage