Identification of a Gene Located at Chromosome 5q21 that Is Mutated in Colorectal Cancers

• DOI: 10.1126/science.1848370
• Publication Date: 2006-10-05T22:10:16Z
• Authors: Kenneth W. Kinzler; Mef C. Nilbert; Bert Vogelstein; Tracy M. Bryan; Daniel B. Levy; Kelly J. Smith; Antonette C. Prei...; Stanley R. Hamilton; Phil Hedge; Alex Markham; Mary Carlson; Geoff Joslyn; Joanna Groden; Ray White; Yoshoi Miki; Yasuo Miyoshi; Isamu Nishisho; Yusuke Nakamura
• Keywords: Base Sequence; Tumor Suppressor Proteins; Molecular Sequence Data; Oligonucleotides; Gene Expression; Proteins; Exons; Polymerase Chain Reaction; Rats; 3. Good health; Adenomatous Polyposis Coli; GTP-Binding Proteins; Sequence Homology, Nucleic Acid; Mutation; Animals; Chromosomes, Human, Pair 5; Humans; Genes, Tumor Suppressor; Amino Acid Sequence; Colorectal Neoplasms

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 ( m utated in c olorectal c ancer), 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.