Novel sequence variants and common recurrent polymorphisms of BRCA2 in Sri Lankan breast cancer patients and a family with BRCA1 mutations

De Silva,Sumadee; Tennekoon,Kamani  H.; Karunanayake,Eric  H.; De Silva,Wasanthi; Amarasinghe,Indrani; Angunawela,Preethika

doi:10.3892/etm.2011.337

Novel sequence variants and common recurrent polymorphisms of BRCA2 in Sri Lankan breast cancer patients and a family with BRCA1 mutations

Authors:
- Sumadee De Silva
- Kamani H. Tennekoon
- Eric H. Karunanayake
- Wasanthi De Silva
- Indrani Amarasinghe
- Preethika Angunawela
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Affiliations: Institute of Bio- chemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo 03, Sri Lanka, Institute of Bio- chemistry, Molecular Biology and Biotechnology, University of Colombo, Colombo 03, Sri Lanka, National Cancer Institute, Maharagama, Sri Lanka, Department of Pathology, Faculty of Medicine, University of Colombo, Colombo 08, Sri Lanka
Published online on: August 17, 2011 https://doi.org/10.3892/etm.2011.337
Pages: 1163-1170

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Abstract

We previously reported BRCA1 mutations and sequence variants in Sri Lankan breast cancer patients. Mutations and sequence variants of the BRCA2 gene were studied in 149 study participants from the same cohort. There were 55 familial and 54 sporadic breast cancer patients, 20 at-risk individuals and 20 healthy controls. Direct sequencing (exon 11) and sequencing of abnormal bands after screening with single-strand conformation polymorphism (remaining exons) were used to detect mutations and sequence variants. Twenty-three sequence variants were found in the BRCA2 gene. Two novel pathogenic frame-shift additions resulting in a premature stop codon (c.2403 insA/exon 11, c.2667 insT/exon 11) were identified. Possibly pathogenic two novel missense mutations (c.1191 A>C/exon 10, c.5695 A>C/exon 11) one novel intronic variant (IVS15-21 insTT), four novel silent mutations (c.969 C>T/exon 9, c.1353 C>T/exon 10, c.2766 A>C/exon 11 and c.7452 A>G/exon 14) and one novel missense mutation (c.971 C>G/exon 9) were observed. One previously reported possibly pathogenic intronic variant (IVS81 G>C) and several previously reported silent mutations, missense mutations, and one 5' UTR polymorphism were detected. Pathogenic and possibly pathogenic mutations were more frequent in the BRCA2 gene among Sri Lankan familial breast cancer patients when compared to our previous findings for the BRCA1 gene.

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