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Series GSE10893 Query DataSets for GSE10893
Status Public on Nov 06, 2011
Title Basal-like Breast Cancer DNA copy number losses identify genes involved in genomic instability, response to therapy, and patient survival
Organism Homo sapiens
Experiment type Expression profiling by array
Genome variation profiling by genome tiling array
Genome variation profiling by SNP array
Summary Breast cancer is a heterogeneous disease with known tumor subtypes. In order to gain insight into the underlying etiologies of these disease subtypes, we first classified tumors according to gene expression intrinsic subtype, and second, identified subtype associated tumor genomic DNA copy number alterations (CNA) using a novel method called SWITCHdna. Most tumor subtypes showed specific CNA with Basal-like breast cancers being the most distinct and associated with loss of RB1, BRCA1, 5q11-35, and showed the greatest overall genomic instability. The common Basal-like CNA of loss of a segment of chromosome 5q11-35 contained at least three genes important for DNA repair (RAD17, RAD50, and RAP80), which were predominantly lost in pairs or all three simultaneously. Loss of two or three of these genes was associated with significantly increased genomic instability as defined by the absolute number of CNA, and poor patient survival . RNAi knockdown of RAD17, or RAD17 and RAD50, in an immortalized HMEC line caused increased sensitivity to a PARP inhibitor, or carboplatin. These data suggest mechanisms for genomic instability in Basal-like breast cancers and a biological rationale for the use of DNA repair inhibitor related therapeutics in this aggressive breast cancer subtype.
 
Overall design 324 Human breast samples by microarray (275 samples from primary sites, 35 from sites of metastasis, and 14 normal tissues). 180 Human breast tumors by aCGH (Illumina).
 
Contributor(s) Weigman VJ, Perou CM
Citation(s) 22048815
Submission date Mar 19, 2008
Last update date Nov 17, 2017
Contact name Charles M. Perou
E-mail(s) cperou@med.unc.edu
Organization name University of North Carolina at Chapel Hill
Department Professor of Genetics, and Pathology & Laboratory Medicine; Lineberger Comprehensive Cancer Center
Street address 12-044 Lineberger Comprehensive Cancer Center CB# 7295
City Chapel Hill
State/province NC
ZIP/Postal code 27599-7264
Country USA
 
Platforms (7)
GPL885 Agilent-011521 Human 1A Microarray G4110A (Feature Number version)
GPL887 Agilent-012097 Human 1A Microarray (V2) G4110B (Feature Number version)
GPL1390 Agilent Human 1A Oligo UNC custom Microarrays
Samples (504)
GSM34423 PB138-Int
GSM34424 BR00-0504
GSM34425 BR00-0284
Relations
BioProject PRJNA107291

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE10893_RAW.tar 11.9 Mb (http)(custom) TAR
Processed data included within Sample table

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