GENETIC ALTERATIONS IN COLORECTAL-CANCER, COMPARATIVE-ANALYSIS OF DELETION EVENTS, AND POINT MUTATIONS

Although data on genetic alterations leading to the development of col or ectal cancer are abundant, no specific genetic alteration, as has b een demonstrated for certain rare tumors such as lymphoma leukemia, or sarcoma, has been shown to be responsible for the development of colo rectal carcinomas. The color ectal cancer phenotype undoubtedly origin ates fr om an accumulation of different genetic alterations, The natur e of these alterations, their order of appearance, and their associati ons vary greatly from one tumor to another, suggesting that the concep t of a unique model of carcinogenesis is not applicable to these tumor s. Mie studied a panel of 40 colorectal rumors in an attempt to identi fy different carcinoma subsets distinguishable by the pattern of genet ic alterations. We examined a series of genetic anomalies frequently i mplicated in the development of colorectal cancer, including generic m aterial loss, demonstrated by loss of heterozygosity on chromosome arm s 1p, 17p, and 18q; mutations of proto-oncogene K-RAS codons 12, 13, a nd 61; and gene TP53 mutations, identified by studying the accumulatio n of the corresponding immunohistochemically detect able protein. Our findings showed an important correlation between the genetic material loss events and an independent distribution of point mutations, which favors the hypothesis of a specific type of genetic instability charac terized by the recurrent loss of chromatin fragments implicated in a s ubset of colorectal cancers. (C) Elsevier Science Inc., 1998.