Abstract P2-10-04: Characterization of Mutations and Sequence Variations in Breast Cancer Susceptibility Gene 2 (BRCA2) in a Group of Breast Cancer Patients in Sri Lanka

Abstract

Abstract Background: Germline mutations in tumour suppressor genes BRCA1 and BRCA2 confer susceptibility to breast and ovarian cancers. Breast cancer is a leading cause of death in women aged 40-60 years in Sri Lanka. Incidence though low in Sri Lanka, compared to the developed world has almost doubled during the last 15 years. BRCA1 mutations and sequence variants in a group of Sri Lankan breast cancer patients have been characterized recently. Here we report mutations and sequence variants of BRCA2 using the same cohort. Methods: A total of 129 patients comprising of 75 familial breast cancer patients (mean age at diagnosis is 44.64 ± 12.7 years) and 54 sporadic breast cancer patients (mean age at diagnosis 49.13 ± 11 years) were analyzed for BRCA2 sequence variants and mutations. 20 healthy controls were used to compare the results of the patients. Genomic DNA from blood samples was isolated and all exons except exon 11 were screened using Single Strand Conformation Polymorphism (SSCP). Samples in which abnormal bands were detected were confirmed by direct sequencing using MegaBACE 1000 automated DNA Sequencer. Exon 11 will be subjected to direct sequencing without SSCP Technique. Representative samples from exons which did not show abnormal bands were also subjected to direct sequencing. Results: To date twelve sequence variants have been found in this study. One reported sequence variant: c.203G>A/exon2 (44 familial and 39 sporadic cases), one novel silent mutation: c.969C>T/exon9, one novel missense mutation: c.971C>G/exon9, and one reported intronic variant: IVS8-1G>C/exon9 (in one familial case each) were detected. In exon 10, three reported missense mutations: c.1093A>C (10 familial cases), c.1342A>T/C (58 familial cases) and c.1352C>T (4 familial cases), two novel silent mutations: c.1191A>C (5 familial cases) and c.1353C>T (1 familial case) and one reported silent mutation: c.1593A>G (5 familial cases) were characterized. In exon 14, one novel silent mutation: c.7452A>G (20 familial cases and 28 sporadic cases) and one reported silent mutation: c.7470A>G (one familial case) were identified. Discussion: Among the BRCA2 exons screened to date, seven six reported sequence variants and five novel mutations have been detected. Out of them one pathogenic mutation (IVS8 1G>C/exon9) found in one familial case and in the same patient two other novel missense and novel silent mutations were detected (c.971C>G/exon9 and c.969C>T/exon9). Studies are in progress to screen the remaining exons of BRCA2 gene in this cohort of breast cancer patients. Data obtained will help in developing an economical screening test for BRCA2 mutations in Sri Lanka. Supported by Sida/Secretariat for Research Cooperation Grant for Molecular Biology and Biotechnology Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-10-04.