American Association for Cancer Research
00085472can121470-sup-tab1-5.pdf (197.39 kB)

Supplementary Tables 1-7 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 - 198K, Table S1. Number of chromosomes in the cell lines according to ATCC description, SKY images, and GAP estimation. Table S2. Tumor ploidy and percentage of genomic states in tumor genome. Table S3. Validation of LSTs by NGS, PCR and Sanger sequencing. Table S4. Final results obtained on the Experimental set of BLCs. Table S5. Final results obtained on the Validation set of BLCs. Table S6. LSTs fit validated rearrangements in triple-negative cell lines. Table S7. LSTs are conserved in xenografts.



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.