Germline Copy Number Variation Analysis in a Cohort of Patients with Hereditary Breast Cancer in Sri Lanka

Abstract

Breast Cancer is one of the common cancers among women in the world. Variants in known cancer predisposing genes (CPGs) explain up to half of the familial clustering in breast cancer, thus, for a substantial fraction of women with breast cancer having a positive family history of cancer, the genetic changes contributing, remains unexplained. The discovery of gene variants to explain this “missing heritability” is of clinical relevance. Hence it is important to find out the presnece of other types of variants, such as copy number variants (CNVs) in such patients. The spectrum of CNVs in the Sri Lankan population has not been described, previously. This study aimed to identify the presence of germline CNVs associated with cancer predisposition in a cohort of patients with hereditary breast cancer in Sri Lanka. SurePrint G3 Human Comparative Genomic Hybridization (CGH) 4x180K Microarray platform was used to detect CNVs in ten patients with breast cancer (55 years of age) with no known family history of cancer were used as controls. Extracted data was processed using Genomoic Workbench v11.0.1.1 software. A total of 141 CNVs in 10 patients were identified. Thirtyseven CNVs were common to both controls and the patients. Out of the 103 unique CNVs, 22 were seen in six affected patients. A 26.37 Kb CNV loss was identified in the APOBEC3 gene cluster, in 2 patients. Furthermore, 37 novel CNVs which were not previously reported in the Data base of Genomic Variants (DGV) were identified. This study shows that CNVs are likely contributors to the breast cancer predisposition in patients affected with breast cancer in this cohort. Further studies have to perform to get a better understanding on the contribution of CNVs to the breast cancer predisposition in the Sri Lankan population.