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Characteristics of MUTYH variants in Japanese colorectal polyposis patients

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Abstract

Background

The base excision repair gene MUTYH is the causative gene of colorectal polyposis syndrome, which is an autosomal recessive disorder associated with a high risk of colorectal cancer. Since few studies have investigated the genotype–phenotype association in Japanese patients with MUTYH variants, the aim of this study was to clarify the clinicopathological findings in Japanese patients with MUTYH gene variants who were detected by screening causative genes associated with hereditary colorectal polyposis.

Methods

After obtaining informed consent, genetic testing was performed using target enrichment sequencing of 26 genes, including MUTYH.

Results

Of the 31 Japanese patients with suspected hereditary colorectal polyposis, eight MUTYH variants were detected in five patients. MUTYH hotspot variants known for Caucasians, namely p.G396D and p.Y179D, were not among the detected variants.Of five patients, two with biallelic MUTYH variants were diagnosed with MUTYH-associated polyposis, while two others had monoallelic MUTYH variants. One patient had the p.P18L and p.G25D variants on the same allele; however, supportive data for considering these two variants ‘pathogenic’ were lacking.

Conclusions

Two patients with biallelic MUTYH variants and two others with monoallelic MUTYH variants were identified among Japanese colorectal polyposis patients. Hotspot variants of the MUTYH gene for Caucasians were not hotspots for Japanese patients.

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Acknowledgements

We thank the patients and their family members for participation in the study.

Funding

This study was supported in part by a Grant-in-aid for the Support Project of the Strategic Research Center in Private Universities from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan awarded to the Saitama Medical University Research Center for Genomic Medicine (S1311002), a Grant supported by the Program for an Integrated Database of Clinical and Genomic Information from Japan Agency for Medical Research and Development (AMED) and the Office of Metropolitan Hospital Management, Tokyo Metropolitan Government for their financial support.

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Author notes

  1. Hidetaka Eguchi, Masakazu Kohda & Yasushi Okazaki

    Present address: Diagnosis and Therapeutics of Intractable Diseases and Intractable Disease Research Center, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, Japan

  2. Yuhki Tada

    Present address: Technology and Development Team for Mammalian Genome Dynamics, RIKEN BioResource Center, 3-1-1 Koyadai, Tsukuba, Ibaraki, Japan

Authors and Affiliations

  1. Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22, Honkomagome, Bunkyo-ku, Tokyo, 113-8677, Japan

    Misato Takao & Tatsuro Yamaguchi

  2. Department of Digestive Tract and General Surgery, Saitama Medical Center, Saitama Medical University, Saitama, Japan

    Misato Takao & Hideyuki Ishida

  3. Department of Clinical Genetics, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Tatsuro Yamaguchi

  4. Hereditary Tumor Research Project, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Tatsuro Yamaguchi

  5. Division of Translational Research, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, Japan

    Hidetaka Eguchi, Yuhki Tada, Masakazu Kohda & Yasushi Okazaki

  6. Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Koichi Koizumi

  7. Department of Pathology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan

    Shin-ichiro Horiguchi

Authors
  1. Misato Takao
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  2. Tatsuro Yamaguchi
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  3. Hidetaka Eguchi
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  4. Yuhki Tada
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  5. Masakazu Kohda
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  7. Shin-ichiro Horiguchi
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  8. Yasushi Okazaki
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  9. Hideyuki Ishida
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Contributions

All authors contributed to this work. MT performed data collection and in silico analysis, and wrote the manuscript; TY performed genetic counseling and wrote the manuscript; HE, YT, MK, YO, and HI performed genetic analysis; KK performed genetic counseling; and SH made histological diagnosis.

Corresponding author

Correspondence to Tatsuro Yamaguchi.

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Conflict of interest

The authors declare that they have no competing interests.

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Takao, M., Yamaguchi, T., Eguchi, H. et al. Characteristics of MUTYH variants in Japanese colorectal polyposis patients. Int J Clin Oncol 23, 497–503 (2018). https://doi.org/10.1007/s10147-017-1234-7

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  • DOI: https://doi.org/10.1007/s10147-017-1234-7

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