title: DNA polymerase beta mutations in human colorectal cancer.
abstract: Increasing numbers of alterations have been found in protooncogenes (e.g., ras, myc), as well as tumor suppressor genes (e.g., p53, Rb) in various types of tumors. The multiple mutations cannot be explained by the spontaneous mutation rate. It has been suggested that mutator phenotypes leading to the accumulation of these mutations may be required in the early stages of tumorigenesis. To test this hypothesis, the entire coding region of DNA polymerase beta, a repair enzyme, mRNA from colorectal tumors, and corresponding normal mucosa were amplified by polymerase chain reaction, cloned, and sequenced. Mutations in the catalytic domain of DNA polymerase beta were detected in colorectal tumor specimens compared to the normal colorectal mucosa, placenta, and blood samples. Since these mutations changed the structure of polymerase beta, it is expected that the efficiency of the DNA repair system would be impaired and thus may account for the high mutation rate observed in colorectal carcinomas.
authors.affiliation: Department of Molecular Biology, Cleveland Clinic Foundation, Ohio 44195.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: U
authors.initials: U
authors.lastname: Patel
authors.forename: L
authors.initials: L
authors.lastname: Ghosh
authors.forename: S
authors.initials: S
authors.lastname: Banerjee
mesh_terms: D001483:Base Sequence; D002872:Chromosome Deletion; D002898:Chromosomes, Human, Pair 8; D015179:Colorectal Neoplasms / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004256:DNA Polymerase I / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D005796:Genes; D006801:Humans; D007413:Intestinal Mucosa / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction
chemical_list: D004273:DNA, Neoplasm; D009838:Oligodeoxyribonucleotides; D004247:DNA; D004256:DNA Polymerase I