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Title: Concurrent DNA copy number alterations and mutations in genes related to maintenance of genome stability in uninvolved glandular tissue from breast cancer patients      
availability:
available
aggregation:
instance of dataset
privacy:
not applicable
refinement:
curated
dateReleased:
08-19-2015
ID:
E-GEOD-63623
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. Characterization of gross genomic alterations (>500 kbp) in uninvolved glandular tissue from 59 breast cancer patients and in the matched samples of primary tumors and lymph node metastases. Corresponding peripheral blood lekocyte DNA, a pool of female DNA (Promega), or uninvolved glandular tissue DNA was used as reference. No biological replicates are included.
keywords:
comparative genomic hybridization by array
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Array Express
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accessURL: https://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-63623
format:
JSON
storedIn:
OmicsDI
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accessType:
download
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primary:
false
accessURL: www.omicsdi.org/ws/dataset/arrayexpress-repository/E-GEOD-63623.json
format:
XML
storedIn:
OmicsDI
qualifier:
not compressed
accessType:
download
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none
authentication:
none
primary:
false
accessURL: http://www.omicsdi.org/ws/dataset/arrayexpress-repository/E-GEOD-63623.xml
ID:
SCR:014747
name:
Omics Discovery Index
abbreviation:
OmicsDI
homePage: http://www.omicsdi.org/