Comment[ArrayExpressAccession]	E-GEOD-43837
MAGE-TAB Version	1.1										
Public Release Date	2014-04-24
Investigation Title	A BRCA1 Deficient-Like Signature is Enriched in Breast Cancer Brain Metastases										
Comment[Submitted Name]	A BRCA1 Deficient-Like Signature is Enriched in Breast Cancer Brain Metastases
Experiment Description	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. Gene expression of 19 HER2+ human breast cancer brain metastases was compared with gene expression of 19 HER2+ nonmetastatic primary human breast tumors.										
Term Source Name	ArrayExpress	EFO
Term Source File	http://www.ebi.ac.uk/arrayexpress/	http://www.ebi.ac.uk/efo/efo.owl									
Person Last Name	Wittner	McMullin	Wittner	Yang	Singavarapu	Moulis	Lee	Aldape	Steeg	Ramaswamy	Sgroi
Person First Name	Ben	Ryan	Ben	Chunwei	Raj	Sharon	Jeongeun	Kenneth	Patricia	Sridhar	Dennis
Person Mid Initials	S.	P	S					D	S		C
Person Email	wittner.ben@mgh.harvard.edu										
Person Affiliation	Massachusetts General Hospital										
Person Address	Center for Cancer Research, Massachusetts General Hospital, 185 Cambridge St., Boston, MA, USA										
Person Roles	submitter										
Protocol Name	P-GSE43837-1	P-GSE43837-5	P-GSE43837-6	P-GSE43837-2	P-GSE43837-3	P-GSE43837-4	P-GSE43837-7				
Protocol Description	MAS5.0 as implemented by Bioconductor package simpleaffy, version 2.14.05. ID_REF =  VALUE = Transcript abundance (MAS5.0 signal, not logged)	According to manufacturer's instructions (Affymetrix, Santa Clara, CA, USA).	According to manufacturer's instructions (Affymetrix, Santa Clara, CA, USA).	The 19 HER2+ breast cancer brain metastatic specimens were fresh-frozen biopsies obtained from the M.D. Anderson Cancer Center between 1998 and 2001. The HER2+ primary breast cancer specimens were fresh-frozen biopsies obtained from the Massachusetts General Hospital in 2006.	Not applicable.	4,000–5,000 malignant epithelial cells were procured by laser capture microdissection using a PixCell IIe system (Molecular Devices, Mountain View, CA, USA) as described in PubMed ID: 19187537. Total RNA was isolated from captured cells using the PicoPure RNA isolation kit (Molecular Devices), then amplified by T7 RNA amplification (RiboAmp; Molecular Devices).	According to manufacturer's instructions (Affymetrix, Santa Clara, CA, USA). The scanner model used to scan the arrays was an Affymetrix GeneChip Scanner 3000-7G.				
Protocol Type	normalization data transformation protocol	labelling protocol	hybridization protocol	sample treatment protocol	growth protocol	nucleic acid extraction protocol	array scanning protocol				
Experimental Factor Name	ER STATUS	DISEASE STATE	AGE	ORGANISM PART							
Experimental Factor Type	er status	disease state	age	organism part							
Comment[SecondaryAccession]	GSE43837										
Comment[GEOReleaseDate]	2014-04-24										
Comment[ArrayExpressSubmissionDate]	2013-01-28										
Comment[GEOLastUpdateDate]	2014-04-25										
Comment[AEExperimentType]	transcription profiling by array										
SDRF File	E-GEOD-43837.sdrf.txt