Purpose: The biallelic inactivation of the 8-hydroxyguanine repair gene MUTYH leads to MUTYH-associated polyposis (MAP), which is characterized by colorectal multiple polyps and carcinoma(s). However, only limited information regarding MAP in the Japanese population is presently available. Since early-onset colorectal cancer (CRC) is a characteristic of MAP and might be caused by the inactivation of another 8-hydroxyguanine repair gene, OGG1, we investigated whether germline MUTYH and OGG1 mutations are involved in early-onset CRC in Japanese patients.
Methods: Thirty-four Japanese patients with early-onset CRC were examined for germline MUTYH and OGG1 mutations using sequencing.
Results: Biallelic pathogenic mutations were not found in any of the patients; however, a heterozygous p.Arg19∗ MUTYH variant and a heterozygous p.Arg109Trp MUTYH variant were detected in one patient each. The p.Arg19∗ and p.Arg109Trp corresponded to p.Arg5∗ and p.Arg81Trp, respectively, in the type 2 nuclear-form protein. The defective DNA repair activity of p.Arg5∗ is apparent, while that of p.Arg81Trp has been demonstrated using DNA cleavage and supF forward mutation assays.
Conclusion: These results suggest that biallelic MUTYH or OGG1 pathogenic mutations are rare in Japanese patients with early-onset CRC; however, the p.Arg19∗ and p.Arg109Trp MUTYH variants are associated with functional impairments.
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http://dx.doi.org/10.1155/2014/617351 | DOI Listing |
Nat Commun
December 2024
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT, 05405, USA.
8-oxoguanine (8-oxoG) is a common oxidative DNA lesion that causes G > T substitutions. Determinants of local and regional differences in 8-oxoG-induced mutability across genomes are currently unknown. Here, we show DNA oxidation induces G > T substitutions and insertion/deletion (INDEL) mutations in human cells and cancers.
View Article and Find Full Text PDFJ Phys Chem B
December 2024
Department of Chemistry and Institute of Functional Materials, Pusan National University, Busan 46241, South Korea.
Human 8-oxoguanine DNA -glycosylase 1 (hOGG1) is an essential enzyme in DNA repair, responsible for recognizing and excising 8-oxoguanine (8OG), the lesion resulting from oxidative damage to guanine (G). By removing 8OG, hOGG1 prevents mutations like G-to-T transversions, maintains genomic stability, and reduces the risk of cancer and other diseases. Structural studies of hOGG1 bound to DNA have shown that lesion recognition occurs through base eversion from the DNA helix and hOGG1 finger residue insertion into the DNA helix.
View Article and Find Full Text PDFTalanta
February 2025
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, China. Electronic address:
Commun Biol
September 2024
Department of Structural Biology, Van Andel Institute, Grand Rapids, MI, USA.
Mol Oral Microbiol
December 2024
Division of Microbiology and Molecular Genetics, School of Medicine, Loma Linda University, Loma Linda, California, USA.
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