Abstract：
:BRCA1 inactivation is a frequent event in basal-like breast carcinomas (BLC). However, BRCA1 can be inactivated by multiple mechanisms and determining its status is not a trivial issue. As an alternate approach, we profiled 65 BLC cases using single-nucleotide polymorphism arrays to define a signature of BRCA1-associated genomic instability. Large-scale state transitions (LST), defined as chromosomal break between adjacent regions of at least 10 Mb, were found to be a robust indicator of BRCA1 status in this setting. Two major ploidy-specific cutoffs in LST distributions were sufficient to distinguish highly rearranged BLCs with 85% of proven BRCA1-inactivated cases from less rearranged BLCs devoid of proven BRCA1-inactivated cases. The genomic signature we defined was validated in a second independent series of 55 primary BLC cases and 17 BLC-derived tumor cell lines. High numbers of LSTs resembling BRCA1-inactivated BLC were observed in 4 primary BLC cases and 2 BLC cell lines that harbored BRCA2 mutations. Overall, the genomic signature we defined predicted BRCA1/2 inactivation in BLCs with 100% sensitivity and 90% specificity (97% accuracy). This assay may ease the challenge of selecting patients for genetic testing or recruitment to clinical trials of novel emerging therapies that target DNA repair deficiencies in cancer.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Popova T,Manié E,Rieunier G,Caux-Moncoutier V,Tirapo C,Dubois T,Delattre O,Sigal-Zafrani B,Bollet M,Longy M,Houdayer C,Sastre-Garau X,Vincent-Salomon A,Stoppa-Lyonnet D,Stern MHdoi
10.1158/0008-5472.CAN-12-1470subject
Has Abstractpub_date
2012-11-01 00:00:00pages
5454-62issue
21eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-12-1470journal_volume
72pub_type
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