Mismatch repair gene pathogenic germline variants in a population-based cohort of breast cancer

AbstractThe advent of gene panel testing is challenging the previous practice of using clinically defined cancer family  syndromes to inform single-gene genetic screening. Individual and family cancer histories that would have previously indicated testing of a single gene or a small number of related genes are now, increasingly, leading to screening across gene panels that contain larger numbers of genes. We have a pplied a gene panel test that included four DNA mismatch repair (MMR) genes (MLH1,MSH2,MSH6 andPMS2) to an Australian population-based case –control-family study of breast cancer. Altogether, eight pathogenic variants in MMR genes were identified: six in 1421 case-families (0.4%, 4MSH6 and 2PMS2) and two in 833 control-families (0.2%, one each ofMLH1 andMSH2). This testing highlights the current and future challenges for clinical genetics in the context of anticipated gene panel-based population-based screening that includes the MMR genes. This testing is likely to provide additional opportunities for cancer prevention via cascade testing for Lynch syndrome and precision medicine for breast cancer treatment.
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research