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Science 15 March 1991:
Vol. 251. no. 4999, pp. 1366 - 1370
DOI: 10.1126/science.1848370
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Articles

Science, Vol 251, Issue 4999, 1366-1370
Copyright © 1991 by American Association for the Advancement of Science

articles

Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers

KW Kinzler, MC Nilbert, B Vogelstein, TM Bryan, DB Levy, KJ Smith, AC Preisinger, Hamilton SR, P Hedge, A Markham, and al. et

Molecular Genetics Laboratory, Johns Hopkins Oncology Center, Baltimore, MD 21231.

Recent studies have suggested the existence of a tumor suppressor gene located at chromosome region 5q21. DNA probes from this region were used to study a panel of sporadic colorectal carcinomas. One of these probes, cosmid 5.71, detected a somatically rearranged restriction fragment in the DNA from a single tumor. Further analysis of the 5.71 cosmid revealed two regions that were highly conserved in rodent DNA. These sequences were used to identify a gene, MCC (mutated in colorectal cancer), which encodes an 829-amino acid protein with a short region of similarity to the G protein-coupled m3 muscarinic acetylcholine receptor. The rearrangement in the tumor disrupted the coding region of the MCC gene. Moreover, two colorectal tumors were found with somatically acquired point mutations in MCC that resulted in amino acid substitutions. MCC is thus a candidate for the putative colorectal tumor suppressor gene located at 5q21. Further studies will be required to determine whether the gene is mutated in other sporadic tumors or in the germ line of patients with an inherited predisposition to colonic tumorigenesis.


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