APC – Sarcoma

APC (adenomatous polyposis coli) has a well-established role in colorectal tumorigenesis, but its involvement in primary sarcomas is minimal. A broad somatic screen of 47 sarcoma specimens revealed no truncating or missense mutations in the APC mutation cluster region, suggesting the gene does not commonly contribute to sarcoma pathogenesis (PMID:9083931). In a clinical genetic screening of 169 adult sarcoma patients, three independent probands were found to carry germline APC variants alongside mutations in MLH1 and MSH2, although no additional segregation data were reported and none of these families fit classic familial adenomatous polyposis criteria (PMID:26628864).

Overall, the current human genetic evidence for APC in sarcoma meets Limited validity: only three unrelated germline carriers without segregation or functional correlation. Functional data in sarcoma models are lacking and somatic surveys refute a driver role. Further comprehensive family studies and mechanistic work would be required to clarify any rare predisposition. Key take-home: APC alterations do not appear to be a major contributor to sarcoma development in sporadic or familial contexts.

References

• Journal of molecular medicine (Berlin, Germany) • 1997 • Molecular analysis of the adenomatous polyposis coli gene in sarcomas, hematological malignancies and noncolonic, neoplastic tissues. PMID:9083931
• Current oncology (Toronto, Ont.) • 2015 • Using a family history questionnaire to identify adult patients with increased genetic risk for sarcoma. PMID:26628864

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