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.

腺瘤性息肉病（APC）基因的失活是家族性腺瘤性息肉病（FAP）患者的起始事件。多达90％的FAP患者表现出肠肿瘤和其他结肠外恶性肿瘤，包括肝母细胞瘤，类胶质瘤和脑癌。APC突变小鼠（Apc ^{Min / +}小鼠）在肠道中出现良性息肉。据报道，少数Apc ^{Min / +}小鼠会患上乳腺癌。在这里，我们发现大约1.6％的Apc ^{Min / +}小鼠患有皮肤肿瘤。结果表明，这些皮肤肿瘤不是来源于肠腺瘤。Apc ^{Min / +}小鼠和Apc皮肤肿瘤的测序^{最小/ +}小鼠皮肤。数据显示与对照相比，皮肤肿瘤中的体细胞突变和基因表达水平发生了很大变化。同样，在癌症数据库中，非黑色素瘤皮肤癌患者中APC突变占27％，并且在所有患者中均观察到上述两个基因突变共存。此外，使用基因突变试剂（DMBA）处理的装甲运兵^{最小/ +}小鼠的皮肤，皮肤上皮和腺体增生开始装甲运兵^{最小/ +}小鼠。这些发现表明，体细胞突变击中种系突变会增加肿瘤发生率，这表明如果在一个体内存在种系突变，则应避免体细胞突变。