Takami K, Yana I, Kurahashi H, Nishisho I
Department of Medical Genetics, Osaka University Medical School, Japan.
Southeast Asian J Trop Med Public Health. 1995;26 Suppl 1:190-6.
Recent advances in molecular genetics have revealed that multiple genetic alterations including activation of oncogenes and inactivation of tumor suppressor genes are required for tumor development and progression. Tumorigenesis of colorectal cancer, in which most cancers are considered to arise from preceding benign adenomas, has been well documented at the molecular level. Familial adenomatous polyposis (FAP), which is characterized by the development of hundreds to thousands of adenomatous polyps in the colon and rectum, one or more of which can progress to cancer if left without surgical treatment, is a good model for elucidation of genetic alterations involved in colorectal tumorigenesis. The adenomatous polyposis coli (APC) gene responsible for FAP was isolated in 1991, and germinal and somatic mutations of the APC gene have been identified. Moreover, activation of K-ras oncogene and inactivation of several tumor suppressor genes such as MCC, p53, and DCC are supposed to play important roles at specific stages of colorectal tumorigenesis. More recently, two genes, MSH2 and MLH1, responsible for hereditary non-polyposis colorectal cancer (HNPCC) have been identified. Thus the molecular mechanism of colorectal tumorigenesis now seems to be more complicated than has been supposed.
分子遗传学的最新进展表明，肿瘤的发生和发展需要多种基因改变，包括癌基因的激活和抑癌基因的失活。大多数结肠癌被认为起源于先前的良性腺瘤，其肿瘤发生在分子水平上已有充分记录。家族性腺瘤性息肉病（FAP）的特征是在结肠和直肠中出现数百至数千个腺瘤性息肉，如果不进行手术治疗，其中一个或多个息肉可能会发展为癌症，它是阐明结直肠癌发生过程中涉及的基因改变的良好模型。1991年分离出了导致FAP的腺瘤性息肉病 coli（APC）基因，并已鉴定出该基因的胚系和体细胞突变。此外，K-ras癌基因的激活以及MCC、p53和DCC等几种抑癌基因的失活被认为在结直肠癌发生的特定阶段起重要作用。最近，已鉴定出两个与遗传性非息肉病性结直肠癌（HNPCC）相关的基因，即MSH2和MLH1。因此，结直肠癌发生的分子机制现在似乎比之前认为的更为复杂。
