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.
Authors
- Dushyant Singh Dahiya (ORCID: https://orcid.org/0000-0002-8544-9039)
- Yash Shah (ORCID: https://orcid.org/0000-0001-7285-7773)
- Ganesh Kumar (ORCID: https://orcid.org/0000-0003-0747-8042)
- Sumant Inamdar
- Ravi Patel
Institutions
- 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)
Publication Details
- 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
- Field-Weighted Citation Impact
- 0.00