Abstract LB-329: Copy number variations associated with hereditary breast and colorectal carcinomas

Abstract

Abstract Breast and colorectal cancer are the most common malignant neoplasia in the world. In Brazil, breast cancer is the first malignant neoplasia and colorectal cancer, the third. It is estimated that among 5–10% of all cancer cases are hereditary. Copy number alterations (CNVs) may affect genes associated to cancer, providing an explanation for high risk cancer families. In this study, 57 individuals with Hereditary Breast and Colorectal Carcinoma were screened for BRCA1, BRCA2, CHEK2, TP53, MLH1 and MSH2 mutations by Sanger's sequencing method. In addition, copy number alterations were evaluated by array comparative genomic hybridization (aCGH) using a platform of 4×180K (Agilent). The data were compared with the Database of Genomic Variations (DGV;http://projects.tcag.ca/variation/) and with a reference dataset obtained from 82 healthy Brazilian individuals. Genomic data were extracted and flagged with Feature Extraction software and analyzed using Genomic Workbench Standard 5.0.14, statistical algorithm ADM2 and sensitivity threshold of 6.7. Alterations identified in more than 5% of the control women were excluded from both groups. The patients were divided into two groups: 28 patients with breast or colorectal cancer (group 1) and 29 women with breast and colorectal carcinoma (group 2). Sixteen relatives from seven patients were also evaluated by aCGH. All patients were negative for BRCA1, BRCA2, CHEK2, TP53, MLH1 and MSH2 pathogenetic mutations. However, the aCGH analysis detected a total of 569 chromosomal alterations in healthy Brazilian dataset (in average 6.8/individual), 170 CNVs (in average 6.1/individual) in group 1, and 232 (in average 8.0/individual) in group 2 patients. Forty-five and 63 chromosomal regions altered were detected in group 1 and 2, respectively. Nineteen chromosomal alterations were common to both groups. Mapped on these regions altered, it was identified 28 microRNAs. Ten specific chromosomal alterations were found in patients and their relatives; seven of them were losses involving genes not previously described in breast and colorectal carcinomas patients. Our results suggest that these chromosomal regions harbor genes associated with Hereditary Breast and Colorectal Carcinomas. Financial Support: FAPESP (2008/57887–9) and CNPq (57589/2008–9) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-329. doi:10.1158/1538-7445.AM2011-LB-329