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Somatic mutations and genetic polymorphisms of the PPP1R3 gene in patients with several types of cancers

Oncogene volume 19, pages 836–840 (2000)Cite this article

Abstract

Recently, we found nonsense and missense mutations of the PPP1R3 (protein phosphatase 1, regulatory subunit 3) gene in diverse human cancer cell lines and primary lung carcinomas, indicating that PPP1R3 functions as a tumor suppressor in human carcinogenesis. In this study, to assess the prevalence of PPP1R3 mutations in human primary cancers and the genetic diversity of the PPP1R3 gene in the human population, somatic mutations and genetic polymorphisms in the PPP1R3 gene were examined in 137 pairs of cancerous and non-cancerous tissues of patients with cancers of colon, ovary, and liver. Five somatic mutations including two missense mutations were detected in three cancerous tissues consisting of two colorectal carcinomas and one ovarian carcinoma. Five novel single nucleotide polymorphisms (SNPs) associated with the substitution of amino acids were also identified in cancer patients, in addition to five known nonsynonymous SNPs, including three previously reported ones as having an impact on the susceptibility to insulin resistant disorders. Differences in the activities and properties of multiple PPP1R3 proteins, which are produced in human cells due to variable somatic mutations and genetic polymorphisms in the PPP1R3 gene, can be involved in human carcinogenesis and susceptibility to diseases.

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Acknowledgements

This work was supported in part by a Grant-in-Aid from the Ministry of Health and Welfare for the 2nd-term Comprehensive 10-Year Strategy for Cancer Control, a Grant-in-Aid from the Ministry of Health and Welfare for Research on Human Genome and Gene Therapy, and Grants-in-Aid from the Ministry of Health and Welfare and from the Ministry of Education, Science, Sports and Culture of Japan. The authors thank staff members of National Cancer Center Hospital, Pathology Division of National Cancer Center Research Insititue, Obstetrics/Gynecology and Pathology Departments of the Jikei University School of Medicine, and 2nd Surgery Department of Gunma University School of Medicine for providing tumor specimens and pathological diagnosis. DLD-1, LoVo, HCT116, and HCT15 were provided by Dr M Perucho (La Jolla Cancer Research Center, Burnham Institute, CA, USA). A2780 was provided by Dr E Reed (National Cancer Institute, National Institutes of Health, Bethesda, MD, USA). SKOV3, SW626, and OV1063 were obtained from the American Type Culture Collection (ATCC). S Takakura and K Shimizu are recipients of the Research Resident Fellowship from the Foundation for Promotion of Cancer Research.

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Authors and Affiliations

  1. Biology Division, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo, 1040045, Japan

    Satoshi Takakura, Takashi Kohno, Kimihiro Shimizu & Jun Yokota

  2. Department of Obstetrics and Gynecology, The Jikei University School of Medicine, 25-8, Nishi-Shinbashi 3-chome, Minato-ku, Tokyo, 1058461, Japan

    Satoshi Takakura & Aikou Okamoto

  3. Second Department of Surgery, Gunma University School of Medicine, 39-15, Showa-machi 3-chome, Maebashi, 3718511, Japan

    Kimihiro Shimizu & Susumu Ohwada

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  1. Satoshi Takakura
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Takakura, S., Kohno, T., Shimizu, K. et al. Somatic mutations and genetic polymorphisms of the PPP1R3 gene in patients with several types of cancers. Oncogene 19, 836–840 (2000). https://doi.org/10.1038/sj.onc.1203388

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