Aggressive Right-Sided Colon Cancer in a Young Adult: Triple-Whammy Mutations (POLE, KRAS, BRCA1/2) Highlight Emerging Genetic Associations

BRCA mutations are well established in breast and ovarian cancers and increasingly recognized in colorectal cancer (CRC), particularly <i>BRCA1</i>. Dual <i>BRCA1/2</i> pathogenic variants in CRC remain exceptionally rare. We report a case of early-onset CRC in a young male harboring pathogenic variants in <i>BRCA1</i>, <i>BRCA2</i>, and <i>POLE</i>, 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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Journal
ACG Case Reports Journal
Published
2026-02-01
DOI
https://doi.org/10.14309/crj.0000000000002016
Primary Topic
PARP inhibition in cancer therapy
Type
article
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article

Aggressive Right-Sided Colon Cancer in a Young Adult: Triple-Whammy Mutations (POLE, KRAS, BRCA1/2) Highlight Emerging Genetic Associations

Dushyant Singh Dahiya, Yash Shah, Ganesh Kumar, Sumant Inamdar et al.
ACG Case Reports Journal
PARP inhibition in cancer therapy
article

Aggressive Right-Sided Colon Cancer in a Young Adult: Triple-Whammy Mutations (POLE, KRAS, BRCA1/2) Highlight Emerging Genetic Associations

Dushyant Singh Dahiya, Yash Shah, Ganesh Kumar, Sumant Inamdar, Ravi Patel
article en

Abstract

BRCA mutations are well established in breast and ovarian cancers and increasingly recognized in colorectal cancer (CRC), particularly <i>BRCA1</i>. Dual <i>BRCA1/2</i> pathogenic variants in CRC remain exceptionally rare. We report a case of early-onset CRC in a young male harboring pathogenic variants in <i>BRCA1</i>, <i>BRCA2</i>, and <i>POLE</i>, 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.

ACG Case Reports JournalVol. 13(2)
Trinity Health (US), University of Kansas (US), Wayne State University (US), Chandka Medical College (PK), Motility (United States) (US), University of Arkansas for Medical Sciences (US)
Good health and well-being
Openalex Percentile: Top 47%
PARP inhibition in cancer therapy
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Aggressive Right-Sided Colon Cancer in a Young Adult: Triple-Whammy Mutations (POLE, KRAS, BRCA1/2) Highlight Emerging Genetic Associations — Dushyant Singh Dahiya, Yash Shah, et al. · ACG Case Reports Journal (2026) | TGRS Research Map | TGRS