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Series GSE43837 Query DataSets for GSE43837
Status Public on Apr 24, 2014
Title A BRCA1 Deficient-Like Signature is Enriched in Breast Cancer Brain Metastases
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Purpose: There is an unmet clinical need for biomarkers to identify breast cancer patients who are at increased risk of developing brain metastases. The objective is to identify gene signatures and biological pathways associated with HER2+ brain metastasis.

Experimental Design: Gene expression of 19 HER2+ breast cancer brain metastases was compared with HER2+ nonmetastatic primary tumors. Gene Set Enrichment Analysis was used to identify a signature, which was evaluated for correlation with BRCA1 mutation status and clinical outcome using published microarray datasets and for correlation with pharmacological inhibition by a PARP inhibitor and temozolomide using published microarray datasets of breast cancer cell lines.

Results: A BRCA1 Deficient-Like (BD-L) gene signature is significantly correlated with HER2+ metastases in both our and an independent cohort. BD-L signature is enriched in BRCA1 mutation carrier primary tumors and HER2-/ER- sporadic tumors, but high values are found in a subset of ER+ and HER2+ tumors. Elevated BD-L signature in primary tumors is associated with increased risk of overall relapse, brain relapse, and decreased survival. The BD-L signature correlates with pharmacologic response to PARP inhibitor and temozolomide in two independent microarray datasets, and the signature outperformed four published gene signatures of BRCA1/2 deficiency.

Conclusions: The BD-L signature is enriched in breast cancer brain metastases and identifies a subset of primary tumors with increased propensity for brain metastasis. Furthermore, this signature may serve as a biomarker to identify sporadic breast cancer patients who could benefit from a therapeutic combination of PARP inhibitor and temozolomide.
 
Overall design Gene expression of 19 HER2+ human breast cancer brain metastases was compared with gene expression of 19 HER2+ nonmetastatic primary human breast tumors.
 
Contributor(s) McMullin RP, Wittner BS, Yang C, Singavarapu R, Moulis S, Lee J, Aldape KD, Steeg PS, Ramaswamy S, Sgroi DC
Citation(s) 24625110
Submission date Jan 28, 2013
Last update date Jul 24, 2014
Contact name Ben S. Wittner
E-mail(s) wittner.ben@mgh.harvard.edu
Organization name Massachusetts General Hospital
Department Center for Cancer Research
Lab Lawrence
Street address 149 13th Street
City Boston
State/province MA
ZIP/Postal code 02129
Country USA
 
Platforms (1)
GPL1352 [U133_X3P] Affymetrix Human X3P Array
Samples (38)
GSM1071862 brain_met_J3
GSM1071863 brain_met_BT25
GSM1071864 brain_met_J12
Relations
BioProject PRJNA187530

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
GSE43837_RAW.tar 186.0 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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