The Somatic Mutation Hit on Top of Genetic APC mutations Cause Skin Tumor

摘要

Inactivation of the adenomatous polyposis coli (APC) gene is the initiating event in familial adenomatous polyposis (FAP) patients. Up to 90% of FAP patients show intestinal tumors and other extracolonic malignancies including hepatoblastomas, desmoid tumors, and brain cancer. APC mutation mice (Apc(Min/+) mice) develop benign polyps in the intestinal tract. It has been reported that small numbers of Apc(Min/+) mice develop breast carcinomas. Here, we found that approximately 1.6% of Apc(Min/+) mice suffered skin neoplasm. The results demonstrated that these skin tumors are not derived from intestinal adenomas. Sequencing of skin tumors of Apc(Min/+) mice and Apc(Min/+) mice skin. The data showed that somatic mutations and gene expression levels changed greatly in skin tumors compared to control. Similarly, APC mutation accounts for 27% in the patients of nonmelanoma skin carcinomas in cancer database, and two above genes mutation coexist was observed in all patients. Furthermore, using gene mutation reagent (DMBA)-treated Apc(Min/+) mice skin, the skin epithelium and glandular begin hyperplasia in Apc(Min/+) mice. These findings revealed that the somatic mutation hit on the germline mutation increase the tumor incidence, suggesting that the somatic mutation should be avoided if the germline mutation exists in one body.