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Coexistence of APC and KRAS mutations in familial adenomatous polyposis and endometrial cancer: A mini-review with case-based perspective

2025-07-18
(Press-News.org) Researchers have discovered an unusual case where two well-known cancer-related mutations—APC and KRAS—coexisted in a woman with familial adenomatous polyposis (FAP) and a history of endometrial cancer. This case may reveal new insights into how different genetic mutations can cooperate across organ systems to promote cancer development.

FAP is a rare inherited condition that causes hundreds to thousands of polyps to grow in the colon, significantly increasing colorectal cancer risk. It is primarily caused by mutations in the APC gene, which normally acts to suppress tumors by regulating cell growth through the Wnt/β-catenin pathway.

In contrast, KRAS mutations, particularly the p.G12V variant, are common in sporadic colorectal and endometrial cancers, where they hyperactivate the RAS/MAPK signaling pathway to drive cell proliferation. While both mutations are well-studied individually, their coexistence in a single patient with FAP and endometrial cancer is extremely rare.

“This is the first case we’ve encountered where a pathogenic APC frameshift mutation (p.G1357Efs*58) and an oncogenic KRAS p.G12V mutation were found together in a microsatellite-stable tumor background,” said lead researcher Dr. Haibo Lan. “It offers a real-world opportunity to understand how disruptions in both Wnt and MAPK signaling could interact to influence tumor behavior beyond the colon.”

The patient had undergone successful treatment for endometrial cancer years before presenting with colorectal polyps. Genetic testing on these polyps revealed the dual mutation. Despite a lack of family history, the case highlights the potential for de novo mutations or underrecognized genetic risk factors.

The findings support a growing body of research suggesting that APC mutations may play a broader role in tumors beyond the gut. According to co-author Dr. Tongchuan Yin, this dual-mutation pattern may signal a more aggressive disease course and warrants multidisciplinary surveillance, including gynecological and gastrointestinal follow-up, genetic counseling, and consideration of chemoprevention.

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[Press-News.org] Coexistence of APC and KRAS mutations in familial adenomatous polyposis and endometrial cancer: A mini-review with case-based perspective