title: Polymorphisms and probable lack of mutation in a human mutT homolog, hMTH1, in hereditary nonpoliposis colorectal cancer.
abstract: The human MTH1 gene, a homolog of the E. coli mutator gene mutT, encodes 8-oxo-dGTPase that degrades a mutagenic substrate for DNA synthesis. To determine whether this gene is associated with hereditary nonpolyposis colorectal cancer (HNPCC), we examined the hMTH1 sequence in 32 HNPCC cases by means of polymerase chain reaction-single strand conformation polymorphism and sequencing analyses. Three different DNA variants were identified in normal and the corresponding tumor DNA. The first variant, a G to A transition at codon 83, changes valine to methionine and was detected in 9 HNPCC cases. The same change was detected in 5 of 30 unrelated healthy individuals, suggesting that it is not associated with a marked HNPCC predisposition. The second variant is a silent C to T transition at codon 119. Another C to T transition at 31 bp upstream of the beginning of exon 4 was also found. However, specific mutations in hMTH1 were detected in neither normal nor tumor cells from HNPCC patients. These results indicate that hMTH1 is not directly involved in HNPCC.
authors.affiliation: Department of Hygiene and Oncology, Tokyo Medical and Dental University School of Medicine, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Wu
authors.forename: H
authors.initials: H
authors.lastname: Nagasaki
authors.forename: K
authors.initials: K
authors.lastname: Maruyama
authors.forename: Y
authors.initials: Y
authors.lastname: Nakabeppu
authors.forename: M
authors.initials: M
authors.lastname: Sekiguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Yuasa
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D003062:Codon; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D017931:DNA Primers; D045643:DNA Repair Enzymes; D018076:DNA, Complementary; D015252:Deoxyribonucleases, Type II Site-Specific; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins; D005656:Fungal Proteins / Q000235:genetics*; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011755:Pyrophosphatases; D012016:Reference Values; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D012689:Sequence Homology, Nucleic Acid; D013728:Terminator Regions, Genetic
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001426:Bacterial Proteins; D003062:Codon; D017931:DNA Primers; D018076:DNA, Complementary; D029968:Escherichia coli Proteins; D005656:Fungal Proteins; C118806:MTH1 protein, S cerevisiae; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; C048503:ATGCAT-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific; D010744:Phosphoric Monoester Hydrolases; D011755:Pyrophosphatases; C052211:mutT protein, E coli; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes