Case report uncovers triple mutations in early-onset colorectal cancer, suggesting a novel genetic subtype.
BRCA mutations are well established in breast and ovarian cancers and increasingly recognized in colorectal cancer (CRC), particularly BRCA1 . Dual BRCA1/2 pathogenic variants in CRC remain exceptionally rare. We report a case of early-onset CRC in a young male harboring pathogenic variants in BRCA1 , BRCA2 , and POLE , with no personal or familial cancer history. This mutational triad suggests convergence of homologous recombination deficiency and impaired DNA proofreading, resulting in a hypermutated phenotype. The case may represent a novel molecular CRC subtype and underscores the importance of broad-panel germline testing in young patients, with implications for poly (ADP‑ribose) polymerase and immune checkpoint inhibitor therapy.
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Patel et al. (2026) studied this question.
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