American Association for Cancer Research
00085472can121470-sup-fig1-5.pdf (1.71 MB)

Supplementary Figures 1-5 from Ploidy and Large-Scale Genomic Instability Consistently Identify Basal-like Breast Carcinomas with BRCA1/2 Inactivation

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journal contribution
posted on 2023-03-30, 21:20 authored by Tatiana Popova, Elodie Manié, Guillaume Rieunier, Virginie Caux-Moncoutier, Carole Tirapo, Thierry Dubois, Olivier Delattre, Brigitte Sigal-Zafrani, Marc Bollet, Michel Longy, Claude Houdayer, Xavier Sastre-Garau, Anne Vincent-Salomon, Dominique Stoppa-Lyonnet, Marc-Henri Stern

PDF file - 1.7MB, Figure S1. Near-diploid (A) and near-tetraploid (B) profiles and patterns of alteration detected with the GAP method in the series of BLCs (Affymetrix SNP6.0). Figure S2. Four outlying patterns of alteration found in the series of BLCs. Figure S3. Deciphering the cutoff for the �small-scale� variation. Figure S4. LSTs detected in SNP array profile and validated by the NGS, Sanger sequencing and translocation specific PCR. Figure S5. Translocation specific PCR for validation of inter-chromosomal translocations detected by NGS and found within LSTs boundaries.



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. Cancer Res; 72(21); 5454–62. ©2012 AACR.