Một cơ chế cho sự phát triển khối u là sự thất bại để sửa chữa DNA bị hư hỏng. Khô da pigmentosum, ví dụ, là một rối loạn hiếm lặn NST thường gây ra bởi sự thất bại để sửa chữa ADN bị tổn thương bởi ánh sáng cực tím. | Genetics of cancer Another mechanism for tumour development is the failure to repair damaged DNA. Xeroderma pigmentosum for example is a rare autosomal recessive disorder caused by failure to repair DNA damaged by ultraviolet light. Exposure to sunlight causes multiple skin tumours in affected individuals. Many other tumours are found to be associated with instability of multiple microsatellite markers because of a failure to repair mutated DNA containing mismatched base pairs. Microsatellite instability is particularly common in colorectal gastric and endometrial cancers. Hereditary non-polyposis colon cancer HNPCC is due to mutations in genes on chromosomes 2p 2q 3p and 7p. The hMSH2 gene on chromosome 2p represents a mismatch repair gene. Some patients with HNPCC inherit one mutant copy of this gene which is inactivated in all cells. Loss of the other allele loss of heterozygosity in colonic cells leads to an increase in the mutation rate in other genes resulting in the development of colonic cancer. The most commonly altered gene in human cancers is the tumour suppressor gene TP53 which encodes the p53 protein. TP53 mutations are found in about 70 of all tumours. Mutations in the RAS oncogene occur in about one third. Interestingly somatic mutations in the tumour suppressor gene TP53 are often found in sporadic carcinoma of the colon but germline mutation of TP53 responsible for Li-Fraumeni syndrome seldom predisposes to colonic cancer. Similarly lung cancers often show somatic mutations of the retinoblastoma RB1 gene but this tumour does not occur in individuals who inherit germline RB1 mutations. These genes probably play a greater role in progression than in initiation of these tumours. Although caused by mutations in the hMSH2 gene the colonic cancers commonly associated with HNPCC show somatic mutations similar to those found in sporadic colon cancers that is in the adenomatous polyposis coli APC gene K-RAS oncogene and TP53 tumour suppressor. This is .
