Clinical and molecular characterization of variants in the CHEK2 gene in Mexican patients with breast cancer

Background: Breast cancer is the most common and lethal cancer worldwide.Germline variants in high-risk genes have been implicated in the development of this cancer.CHEK2 variants are of interest as cancer predisposition markers, but data are lacking.Objective: To characterize germline variants in CHEK2 in a cohort of Mexican patients with breast cancer.Method: Genomic DNA from 2,165 patients with breast cancer was analyzed using sequencing panels for cancer-associated genes, including CHEK2.Variants of CHEK2 were confirmed by capillary sequencing, annotated, and classified according to American College of Medical Genetics and Genomics (ACMG) guidelines using ClinVar and Franklin.results: Ninety-one patients with breast cancer carried at least one CHEK2 variant, including 32 different variants.Fifty-eight of the 91 patients carried at least one pathogenic or likely pathogenic CHEK2 variant.Clinical evidence allowed us to classify 2 of 10 variants with conflicting interpretations as likely pathogenic.Conclusions: This study demonstrates the spectrum of variants in CHEK2 in patients with breast cancer, which may lead to a better understanding, diagnosis and genetic counseling in this population.