CHEK2 gene in metastatic prostate cancer: A cordial check on DNA damage repair pathway

Abstract

Mutation in homologous recombination repair (HRR) pathway is well established in ovarian cancers. Multiple trials have shown variable efficacy in prostate cancers. Mutations other than BRCA1/BRCA2 have been recently reported in prostate cancers. We describe a unique case of an elderly male with metastatic castration-resistant prostate cancer. He responded to hormonal therapy for 6 months but later progressed. Chemotherapy with docetaxel produced severe side effects in the patient and, thus, was discontinued. Next-generation sequencing was performed on tissue sample which selected a pathogenic mutation (TIER 1) in CHEK2 gene, which is a missense mutation, leading to loss of function of protein. CHEK2 is a cell cycle regulator and a tumor suppressor gene mediating homologous recombinant DNA repair pathway and genetic alterations in it makes tumor susceptible to newer targeted therapies.