Researchers have found the gene that when defective causes apredisposition for hereditary non-polyposis colorectal cancer(HNPCC), which accounts for 6 to 16 percent of all colon cancer.The gene, MSH2, also may be associated with other cancers,including uterine, ovarian and stomach cancer.
Two separate teams of researchers identified the gene's link tocancer and announced their findings at a National Institutes ofHealth press conference last week.
Richard Kolodner of the Dana-Farber Cancer Institute in Bostonand Richard Fishel of the University of Vermont found defectsin a bacterial gene and then found its counterpart in humanDNA. Their work is reported in Friday's issue of Cell. BertVogelstein and Kenneth Kinzler of the Johns Hopkins OncologyCenter headed a team of researchers that found that the MSH2gene is altered in families with HNPCC. They also discoveredthat the alteration involves several mutations. Their researchwill be published in the Dec. 17 issue of Cell.
Two years ago, Vogelstein, Kinzler and others identified thegene associated with a rarer form of inherited colon cancer,familial polyposis, which is caused by production of hundredsof polyps in the intestinal tract. According to the NationalCenter for Human Genome Research, about 1 percent of coloncancer is due to this disorder. About one in 200 people in thegeneral population carries an inherited mutation predisposingthem to HNPCC.
Fishel told BioWorld that the normal functioning of the MSH2gene is important for all cells. He said it is essentially a "spellchecker" for cellular duplication of DNA, recognizing whenportions of the DNA are mismatched. The gene binds to theerrors and inserts the right nucleotide into the DNA. Kinzlersaid that an altered MSH2 gene is truncated or has amino acidsubstitutions in its structure.
Researchers do not know what happens to the functioning of adefective gene. Fishel said it may lose all or a portion of itsfunctioning or it may not elicit a response.
Kolodner emphasized that "for 25 years, basic science labs havebeen working on the DNA repair pathway," so now that the linkbetween this pathway and cancer has been found, "we have anenormous body of knowledge for treating and preventingcancer." Fishel said that usually when cancer genes arediscovered, researchers do not know how the gene causescancer or what a normal gene does in the cell.
The labs are working to develop a diagnostic test that coulddetect the defective gene in a blood sample. Kinzler said itwould six months to a year before a test is available and notedthat companies have expressed interest in the test. The geneticdiagnosis will enable families with a predisposition for coloncancer to find out if they have the gene and need to be closelymonitored for onset of the disease.
The gene may also be a target for colon cancer therapeutics.Fishel said such a therapy would target cells with the alteredgene and kill only those cells.
The two teams of researchers received financial support fromNational Institutes of Health and utilized gene-finding toolsdeveloped by the Human Genome Project. TheVogelstein/Kinzler team, which received funding from theNational Cancer Institute, included researchers from theUniversity of Helsinki, the National Center for Human GenomeResearch, the Fred Hutchinson Cancer Research Center, and theUniversity of Texas Health Science Center, among others. TheFishel/Kolodner team was supported by the National Instituteof General Medical Sciences and the Human Genome Project.
-- Brenda Sandburg News Editor
(c) 1997 American Health Consultants. All rights reserved.