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| 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
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| 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.
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| 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.
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| 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 |
| |
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| Platforms (1) |
| GPL1352 |
[U133_X3P] Affymetrix Human X3P Array |
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| Samples (38)
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| Relations |
| BioProject |
PRJNA187530 |
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