Two genes from a chromosome region previously suspected ininherited colon cancer have been isolated and are indeedmutated in tumors from cancer patients, researchers fromJohns Hopkins University, ICI Pharmaceuticals in Britain, theTokyo Cancer Institute and other Japanese centers report inFriday's issue of Nature. Similar findings are reported by aUniversity of Utah team in this week's issue of Cell.

The researchers are confident that genetic screening for theinherited predisposition will now be possible.

Most colorectal cancers arise from benign tissue tags calledpolyps. An inherited predisposition to polyp formation, calledfamilial adenomatous polyposis, affects one in 5,000Americans, the researchers said.

Recent work had linked genetic changes on chromosome 5 withcolorectal cancer. The researchers cloned part of the region onchromosome 5 that had been linked with the familial disease.Of six genes studied, two were the most likely contributors tothe disease.

The MCC gene, previously identified by its mutation in humancolorectal tumors, was mutated only in non-inherited coloncancers. But the newly cloned APC gene was found with asingle amino acid changed in the sperm and egg cells ofpatients with the familial polyposis.

The APC gene is also mutated in tumor cells from non-inherited colon cancer. The scientists conclude that at leasttwo genes must be involved in familial predisposition tocolorectal cancer.

Unfortunately, the APC gene mutations have so far only beenfound in a small minority of families with the inheritedcondition. Further work is needed to find the mutations inother affected families before screening can become useful forthem as well.

-- Roberta Friedman Special to BioWorld

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