Marcela A. De La Fuente-Hernández, Clínica de Cáncer Hereditario, Instituto Nacional de Cancerología, Ciudad de México, México
Silvia Vidal-Millán, Clínica de Cáncer Hereditario, Instituto Nacional de Cancerología, Ciudad de México, México
Paulina Ma. Núñez-Martínez, Clínica de Cáncer Hereditario, Instituto Nacional de Cancerología, Ciudad de México, México
Yuliana Sánchez-Contreras, Clínica de Cáncer Hereditario, Instituto Nacional de Cancerología, Ciudad de México, México
Verónica Z. Fragoso-Ontiveros, Clínica de Cáncer Hereditario, Instituto Nacional de Cancerología, Ciudad de México, México
Ma. de la Luz Mejía-Aguayo, Clínica de Cáncer Hereditario, Instituto Nacional de Cancerología, Ciudad de México, México
Miguel Á. Sarabia-Sánchez, Investigación Básica, Instituto Nacional de Cancerología, Ciudad de México, México
Abraham Pedroza-Torres, Clínica de Cáncer Hereditario, Instituto Nacional de Cancerología, Ciudad de México, México
Claudia H. Arce-Salinas, Servicio de Tumores Mamarios, Instituto Nacional de Cancerología, Ciudad de México, México
Rosa Ma. Álvarez-Gómez, Departamento de Cuidados Paliativos, Instituto Nacional de Cancerología, Ciudad de México, México
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.
Keywords: Hereditary breast cancer. Germline variants. CHEK2. Next generation sequencing.
