Comment[ArrayExpressAccession]	E-MTAB-3111
MAGE-TAB Version	1.1		
Investigation Title	Genotyping BRCA1 and BRCA2 in genomically unstable glandular tissue from breast cancer patients.		
Comment[Submitted Name]	Genotyping BRCA1 and BRCA2 in genomically unstable glandular tissue from breast cancer patients.
Experiment Description	Somatic mosaicism for DNA copy number alterations (SMC-CNA) is defined as gain or loss of chromosomal segments in mitotic cells within a single organism. As cells harboring SMC-CNA have the potential to undergo clonal expansion, SMC-CNA may be present in a substantial portion of cells in differentiated human tissues and may contribute to the predisposition of these cells to genetic disease including cancer. We characterized gross genomic alterations (>500 kbp) in uninvolved glandular tissue from 59 breast cancer patients and matched samples of primary tumors and lymph node metastases. Array based comparative genomic hybridization experiments showed 10% (6/59) of patients harbored 1 - 359 large SMC-CNA (mean: 1328 kbp; median: 961 kbp) in uninvolved glandular tissue. SMC-CNA were partially recurrent in tumors, albeit with considerable contribution of stochastic SMC-can, indicating genomic destabilization. Therefore, we hypothesized that the observed genomic destabilization is predetermined by mutations in genes related to maintenance of genomic integrity. Targeted resequencing of 301 known predisposition and somatic driver loci revealed mutations in the following genes: BRCA1 (p.Gln1756Profs*74, p.Arg504Cys), BRCA2 (p.Asn3124Ile), NCOR1 (p.Pro1570Glnfs*45), PALB2 (p.Ser500Pro) and TP53 (p.Arg306*). We demonstrated that gross SMC-CNA may be present in a substantial portion of glandular tissue cells, which are  distant from that of the tumor cells, and may co-occur with point mutations in crucial cancer predisposing or somatic driver genes. Taken together, this highlights temporal and spatial neoplastic potential of uninvolved glandular tissue from breast cancer patients.		
Experimental Design	case control design	cell type comparison design	genotype design
Experimental Design Term Source REF	EFO	EFO	EFO
Experimental Design Term Accession Number	EFO_0001427	EFO_0001745	EFO_0001748
Experimental Factor Name	genotype		
Experimental Factor Type	genotype		
Experimental Factor Term Source REF	EFO		
Experimental Factor Term Accession Number	EFO_0000513		
Person Last Name	Piotrowski		
Person First Name	Arkadiusz		
Person Mid Initials			
Person Email	arek.piotrowski@gumed.edu.pl		
Person Phone			
Person Fax			
Person Address	Faculty of Pharmacy Medical University of Gdansk Hallera 107 80-416 Gdansk, Poland		
Person Affiliation	Medical University of Gdansk		
Person Roles	submitter		
Date of Experiment	2014-02-28		
Public Release Date	2015-11-30		
Protocol Name	P-MTAB-42164	P-MTAB-42165
Protocol Type	nucleic acid sequencing protocol	nucleic acid library construction protocol	
Protocol Term Source REF	EFO	EFO	
Protocol Term Accession Number	EFO_0004170	EFO_0004184	
Protocol Description	paired end targeted re-sequencing at minimum of 99x coverage	amplicon based targeted re-sequencing at minimum of 99x coverage; BRCA MASTR Dx; http://www.multiplicom.com/products/brca-mastr-dx	
Protocol Hardware	Illumina MiSeq		
Protocol Software	BaseSpace		
Term Source Name	EFO
Term Source File	http://www.ebi.ac.uk/efo/		
Term Source Version			
Comment[AEExperimentType]	DNA-seq		
Comment[SecondaryAccession]	ERP008772
Comment[SequenceDataURI]	http://www.ebi.ac.uk/ena/data/view/ERR687876-ERR687881
SDRF File	E-MTAB-3111.sdrf.txt