1. Identification of a Gene Located at Chromosome 5q21 that Is Mutated in Colorectal Cancers
- Author
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Mef Nilbert, Isamu Nishisho, Alex Markham, Stanley R. Hamilton, Geoff Joslyn, Ray White, Daniel B. Levy, Yoshoi Miki, Kelly J. Smith, Yasuo Miyoshi, Antoneite C. Preisinger, Yusuke Nakamura, Phil Hedge, Tracy M. Bryan, Kenneth W. Kinzler, Joanna Groden, Bert Vogelstein, and M. Carlson
- Subjects
Tumor suppressor gene ,Molecular Sequence Data ,Oligonucleotides ,Gene Expression ,Molecular cloning ,medicine.disease_cause ,Polymerase Chain Reaction ,Restriction fragment ,GTP-Binding Proteins ,Sequence Homology, Nucleic Acid ,medicine ,Animals ,Humans ,Coding region ,Genes, Tumor Suppressor ,Amino Acid Sequence ,Gene ,Multidisciplinary ,Base Sequence ,biology ,Tumor Suppressor Proteins ,Point mutation ,Proteins ,Exons ,Molecular biology ,Rats ,Adenomatous Polyposis Coli ,Mutation ,biology.protein ,Cancer research ,Cosmid ,Chromosomes, Human, Pair 5 ,Colorectal Neoplasms ,Carcinogenesis - Abstract
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.
- Published
- 1991
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