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Mutations in the RAD54 recombination gene in primary cancers

Oncogene volume 18, pages 3427–3430 (1999)Cite this article

Abstract

Association of a recombinational repair protein RAD51 with tumor suppressors BRCA1 and BRCA2 suggests that defects in homologous recombination are responsible for tumor formation. Also recent findings that a protein associated with the MRE11/RAD50 repair complex is mutated in Nijmegen breakage syndrome characterized by increased cancer incidence and ionizing radiation sensitivity strongly support this idea. However, the direct roles of BRCA proteins and the protein responsible for NBS in recombinational repair are not clear though they are associated with the recombinational repair complexes. Since RAD51 forms a complex with other members of the RAD52 epistasis group and with BRCA proteins, it is reasonable to ask if alterations of members of the RAD52 epistasis group lead to tumor development. Here we describe missense mutations at functional regions of RAD54 and the absence of the wild-type RAD54 expression resulting from aberrant splicing in primary cancers. Since RAD54 is a recombinational protein associated with RAD51, this is the first genetic evidence that cancer arises from a defect in repair processes involving homologous recombination.

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Acknowledgements

We thank T Nishioka for photographic work. This work was supported by Grants-in-Aid for Cancer Research from the Ministry of Education, Science and Culture, Japan, and by Tsuchiya Medical Research Foundation.

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Authors and Affiliations

  1. Department of Molecular Pathology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, 734, Hiroshima, Japan

    Masahiro Matsuda, Kiyoshi Miyagawa & Toshikatsu Fukuda

  2. Department of Developmental Biology and Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, 734, Hiroshima, Japan

    Kiyoshi Miyagawa, Mamoru Takahashi & Kenji Kamiya

  3. Department of Cancer Cytogenetics, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, 734, Hiroshima, Japan

    Nanao Kamada

  4. 2nd Department of Surgery, Hiroshima University School of Medicine, 1-2-3 Kasumi, 734, Minami-ku, Hiroshima, Japan

    Masahiro Matsuda, Mamoru Takahashi, Toshikatsu Fukuda, Tsuyoshi Kataoka, Toshimasa Asahara & Kiyohiko Dohi

  5. 1st Department of Surgery, Kinki University School of Medicine, 377-2 Ohno-higashi, 589, Osaka-sayama, Osaka, Japan

    Hiroki Inui, Masahiro Watatani & Masayuki Yasutomi

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  1. Masahiro Matsuda
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  2. Kiyoshi Miyagawa
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Matsuda, M., Miyagawa, K., Takahashi, M. et al. Mutations in the RAD54 recombination gene in primary cancers. Oncogene 18, 3427–3430 (1999). https://doi.org/10.1038/sj.onc.1202692

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