| Theme | Molecular pathology of colorectal cancer for clinicians | |
|---|---|---|
| Title | Familial adenomatous polyposis: clinical aspects and its responsible gene, the adenomatous polyposis coli gene | |
| Publish Date | 2001/05 | |
| Author | Isamu Nishisho | Chinical Research Institute and Department of Surgery, Osaka National Hospital |
| Author | Hideyuki Mishima | Department of Surgery, Osaka National Hospital |
| Author | Toshimasa Tsujinaka | Chinical Research Institute, Osaka National Hospital |
| [ Summary ] | Familial adenomatous polyposis(FAP) is an autosomal dominant disorder, characterized by development of hundreds or thousands of colorectal adenomas during adolescence and young adulthood. If prophylactic colectomy is not performed, colorectal cancer will develop in virtually all affected individuals before the fifth decade of life. Since most colorectal cancers are considered to arise from preceding benign adenoma, FAP is a good model for elucidating genetic alterations involved in colorectal tumorigenesis. The disorder is caused by inherited germ-line mutation in a putative tumor suppressor gene, the adenomatous polyposis coli(APC) gene. The APC gene has been found to be altered by point mutation, deletion or insertion, resulting in truncation of the APC protein not only in the germ-line of FAP and Gardner's syndrome patients but also somatically in tumors of sporadic colorectal cancer patients. With the understanding that the APC gene is inactivated in the initial stage of multistep colorectal carcinogenesis, the gene is thougth to be a "gatekeeper". The important role of the APC protein is regulation of cytoplasmic free beta-catenin levels. Our genetic analysis of the activation of the K-ras oncogene and inactivation of APC and p53 genes in early colorectal cancers (superficial type) revealed that the APC gene is often inactivated in so-called "de novo" type colorectal cancers. | |