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Aberrant hypermethylation of the CHFR prophase checkpoint gene in human lung cancers

Oncogene volume 21, pages 2328–2333 (2002)Cite this article

Abstract

The CHFR gene, which was recently cloned by Scolnick and Halazonetis in search for a novel mitotic checkpoint gene with fork-head association motifs, has been suggested to play a key role in the mitotic prophase checkpoint. In this study, we demonstrated tumor-specific aberrant hypermethylation of the promoter region of the CHFR gene in a significant fraction of lung cancers in association with loss of detectable levels of CHFR transcripts. Aberrant hypermethylation was observed in seven of 37 primary lung cancer cases. Treatment with the demethylating agent 5-aza-2′-deoxycytidine restored expression of the CHFR gene in lung cancer cell lines exhibiting aberrant hypermethylation and loss of its expression. In contrast, genetic alterations were found to be infrequent in lung cancers. This is the first description of aberrant hypermethylation of the CHFR gene in any type of human cancer, and provides further evidence of the involvement of multiple checkpoint alterations in lung cancer.

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Acknowledgements

We would like to thank Drs Curtis C Harris (National Cancer Institute), LJ Old (Memorial Sloan Kettering Cancer Center), M Akiyama (Radiation Effect Research Foundation) and Y Hayata (Tokyo Medical University) for their generous gifts of cell lines. This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science and Culture of Japan and a Grant-in-Aid for the Second Term Comprehensive Ten-Year Strategy for Cancer Control from the Ministry of Health and Welfare, Japan.

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Authors and Affiliations

  1. Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Kotaro Mizuno, Hirotaka Osada, Hiroyuki Konishi, Yoshio Tatematsu, Yoshitaka Fujii & Takashi Takahashi

  2. Department of Anatomic and Molecular Diagnostic Pathology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Yasushi Yatabe

  3. Department of Thoracic Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, 464-8681, Japan

    Tetsuya Mitsudomi

  4. Department of Surgery II, Nagoya City University School of Medicine, Mizuho-cho, Mizuho-ku, Nagoya, 467-8061, Japan

    Kotaro Mizuno & Yoshitaka Fujii

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  1. Kotaro Mizuno
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  2. Hirotaka Osada
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Correspondence to Takashi Takahashi.

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Mizuno, K., Osada, H., Konishi, H. et al. Aberrant hypermethylation of the CHFR prophase checkpoint gene in human lung cancers. Oncogene 21, 2328–2333 (2002). https://doi.org/10.1038/sj.onc.1205402

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