Germline Pathogenic Variants in Homologous Recombination and DNA Repair Genes in an Asian Cohort of Young-Onset Colorectal Cancer

JNCI Cancer Spectrum
Ming Ren TohJoanne Ngeow

Abstract

Growing evidence suggests a role for cancer susceptibility genes such as BRCA2 and PALB2 in young-onset colorectal cancers. Using a cohort of young colorectal cancer patients, we sought to identify and provide functional evidence for germline pathogenic variants of DNA repair genes not typically associated with colorectal cancer. We recruited 88 patients with young-onset colorectal cancers seen at a general oncology center. Whole-exome sequencing was performed to identify variants in DNA repair and colorectal cancer predisposition genes. Pathogenic BRCA2 and PALB2 variants were analyzed using immunoblot and immunofluorescence on patient-derived lymphoblastoid cells. In general, our cohort displayed characteristic features of young-onset colorectal cancers. Most patients had left-sided tumors and were diagnosed at late stages. Four patients had familial adenomatous polyposis, as well as pathogenic APC variants. We identified 12 pathogenic variants evenly distributed between DNA repair and colorectal cancer predisposition genes. Six patients had pathogenic variants in colorectal cancer genes: APC (n = 4) and MUTYH monoallelic (n = 2). Another six had pathogenic variants in DNA repair genes: ATM (n = 1), BRCA2 (n = 1), PALB2 (n = ...Continue Reading

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Citations

Aug 9, 2018·Occupational and Environmental Medicine·Simona GaetaniMonica Amati
May 19, 2020·Human Molecular Genetics·Arun Mouli KolinjivadiJoanne Ngeow
Aug 4, 2020·International Journal of Cancer. Journal International Du Cancer·Tarryn ShawJoanne Ngeow
Dec 15, 2020·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Masashi FujitaYukihide Momozawa
Nov 12, 2021·Genes, Chromosomes & Cancer·Reger R MikaeelTimothy J Price

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