Loss of heterozygosity at 13q13 and 14q32 predicts BRCA2 inactivation in luminal breast carcinomas. Issue 12 (10th July 2013)

• Record Type: Journal Article
• Authors: Pécuchet, Nicolas; Popova, Tatiana; Manié, Elodie; Lucchesi, Carlo; Battistella, Aude; Vincent‐Salomon, Anne; Caux‐Moncoutier, Virginie; Bollet, Marc; Sigal‐Zafrani, Brigitte; Sastre‐Garau, Xavier; Stoppa‐Lyonnet, Dominique; Stern, Marc‐Henri
• Is Part Of: International journal of cancer. Volume 133:Issue 12(2013:Dec. 15)
• Page Start: 2834
• Page End: 2842
• Publication Date: 2013-07-10
• Subjects: Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.28315
• Languages: English
• ISSNs: 0020-7136

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <italic>BRCA2</italic> is the major high‐penetrance predisposition gene for luminal (estrogen receptor [ER] positive) breast cancers. However, many <italic>BRCA2</italic> mutant carriers lack family history of breast/ovarian cancers and do not benefit from genetic testing. Specific genomic features associated with <italic>BRCA2</italic> inactivation in tumors could help identify patients for whom a genetic test for <italic>BRCA2</italic> may be proposed. A series of ER‐positive invasive ductal carcinomas (IDCs) including 30 carriers of <italic>BRCA2</italic> mutations and 215 control cases was studied by single‐nucleotide polymorphism (SNP) arrays. Cases and controls were stratified by grade and HER2 status. Independently, 7 <italic>BRCA2</italic> and 51 control cases were used for validation. Absolute copy number and Loss of heterozygosity (LOH) profiles were obtained from SNP arrays by the genome alteration print (GAP) method. <italic>BRCA2</italic> tumors were observed to display a discriminatively greater number of chromosomal breaks calculated after filtering out and smoothing <3 Mb variations. This argues for a <italic>BRCA2</italic>‐associated genomic instability responsible for long‐segment aberrations. Co‐occurrence of two genomic features—LOH of 13q13 and 14q32—was found to predict <italic>BRCA2</italic> status with 90% of sensitivity and 87% of specificity in discovery series of high‐grade HER2‐negative IDCs and 100% of sensitivity and 88% of specificity in an independent series of 58 IDCs. Estimated positive predictive value was 17.2% (confidence interval: 6.7–33.5) in the whole series. In conclusion, the simplified <italic>BRCA2</italic> classifier based on the co‐occurrence of LOH at 13q13 and 14q32 could provide an indication to test for <italic>BRCA2</italic> mutation in patients with ER‐positive IDC.</p> </abstract>