Identification of a Gene Located at Chromosome 5q21 That is Mutated in Colorectal Cancers

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...

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Bibliographic Details
Published in:	Science (American Association for the Advancement of Science) Vol. 251; no. 4999; pp. 1366 - 1370
Main Authors:	Kinzler, Kenneth W., Nilbert, Mef C., Vogelstein, Bert, Bryan, Tracy M., Levy, Daniel B., Smith, Kelly J., Preisinger, Antonette C., Hamilton, Stanley R., Hedge, Phil, Markham, Alex, Carlson, Mary, Joslyn, Geoff, Groden, Joanna, White, Ray, Miki, Yoshoi, Miyoshi, Yasuo, Nishisho, Isamu, Nakamura, Yusuke
Format:	Journal Article
Language:	English
Published:	Washington, DC American Society for the Advancement of Science 15-03-1991 American Association for the Advancement of Science The American Association for the Advancement of Science
Subjects:	Adenomatous Polyposis Coli - genetics Amino Acid Sequence Amino acids Animals Base Sequence Biological and medical sciences Cancer Carcinogenesis carcinoma Chromosome mapping Chromosomes Chromosomes, Human, Pair 5 Colorectal cancer Colorectal Neoplasms - genetics Cosmids Digestive system DNA Exons Gastroenterology. Liver. Pancreas. Abdomen Gene Expression Genes Genes, Tumor Suppressor Genetic aspects Genetics GTP-Binding Proteins - metabolism Humans man MCC genes Medical research Medical sciences Molecular Sequence Data Mutation Mutation (Biology) Oligonucleotides - chemistry Open reading frames Polymerase Chain Reaction Proteins - genetics Proteins - metabolism Rats Sequence Homology, Nucleic Acid Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Tumor Suppressor Proteins Tumors Human Gene Nucleotide sequence B5-Chromosome DNA Rectum Homology Tumor Colon Mutation Molecular cloning Suppressor gene
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1
ISSN:	0036-8075 1095-9203
DOI:	10.1126/science.1848370