AB116. Germline mutations of Syk gene associated with breast cancer pathogenesis

Abstract: Spleen tyrosine kinase (Syk) gene encodes a non-receptor type tyrosine kinase which is widely expressed in many cell types and is a known tumor suppressor for human breast carcinomas. Studies have reported that mutations in Syk gene are associated with cell invasion and an increased risk of cancer development. In this study the mutational status of the entire coding region of Syk was analysed in breast cancer patients in Brunei Darussalam. By using Sanger sequencing method, the germ-line mutations of Syk gene in breast cancer patients were identified. Analysis of sequencing result revealed seven previously unreported single nucleotide alterations in the coding region of the Syk gene of which five mutations were observed to be silent mutations. Two silent mutations, c.267C > Y and c.384G > R, were observed in exon 2, while one mutation, c.1320C > Y, was observed in sample exon 9. The remaining 2 silent mutations were c.1752T > Y and c.1800T > Y, observed on exon 11. Two missense variations, namely c.1807G > R and c.1834A > M, were identified in exon 11 of the Syk gene which encodes part of kinase domain of the Syk gene. All of these mutations are reported for the first time in this study. Additionally, substitution and deletion mutations were also detected in the non-coding region of the Syk gene. The importance of these mutations in breast cancer pathogenesis at this stage is not clear and requires further work.

Keywords: Spleen tyrosine kinase (Syk); germline; mutation; breast cancer