Optimization and Validation of Tetra Primer-Amplification Refractory Mutation System-based PCR for Detecting Rare Pathogenic BRCA1 deletions

Abstract

Breast Cancer (BRCA) genes encode for DNA damage repair proteins. BRCA gene mutations have been reported in numerous inherited and sporadic cancers, particularly breast cancer. The presence of pathogenic variants significantly increases cancer susceptibility. However, most mutations remain underdiagnosed in Sri Lanka’s resource-limited settings due to the high cost of sequencing. Hence, this study was designed to develop, optimize and validate a Tetra Primer-Amplification Refractory Mutation System (T-ARMS PCR)-based PCR assay for the detection of three rare, pathogenic BRCA1 deletions.