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Frequent epigenetic silencing of the FHIT gene in penile squamous cell carcinomas

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Abstract

Methylation of normally unmethylated CpG-rich islands in or near the promoter region has been associated with transcriptional inactivation of tumor-suppressor and tumor-related genes in human cancers. However, so far, only a few studies have searched for DNA methylation in penile carcinoma (PC). On the other hand, human papillomavirus (HPV) has been reported to be associated with the pathogenesis of PC. To elucidate the methylation status of PC and HPV infection, the methylation status of eight genes (DAPK, FHIT, MGMT, p14, p16, RAR-β, RASSF1A, and RUNX3), the incidences of the HPV status, and the expression of Fhit protein were examined in 25 PCs. The frequencies of methylation were: 28% for DAPK, 92% for FHIT, 20% for MGMT, 4% for p14, 24% for p16, 24% for RAR-β, 12% for RASSF1A, and 44% for RUNX3. Negative expression of Fhit protein was observed in 22 of the 25 cancers (88%). Among those 22, 20 showed methylation of the FHIT gene. HPV-DNA was detected in three of the 25 cancers (12%). Methylation of FHIT gene was frequently found than HPV infection, therefore methylation of the FHIT gene is suggested to play an important role in the pathogenesis of penile squamous cell carcinoma.

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Acknowledgements

We are grateful to Dr. S. Sasou (Yamagata Prefectural Central Hospital), Dr. S. Arai (Yamagata Prefectural Nihonkai Hospital), Dr. K. Nemoto (Niigata Cancer Center Hospital), and Drs. M. Fukase and S. Uchigasaki (Tsuruoka municipal hospital) for kindly providing the samples.

Conflict of interest statement

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Department of Pathology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata, 990-9585, Japan

    Naoki Yanagawa, Mitsumasa Osakabe & Teiichi Motoyama

  2. Department of Dermatology, Yamagata University School of Medicine, Yamagata, 990-9585, Japan

    Masahiro Hayashi

  3. Division of Pathology, Yamagata Prefectural Central Hospital, Yamagata, 990-2292, Japan

    Gen Tamura

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  1. Naoki Yanagawa
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  2. Mitsumasa Osakabe
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  5. Teiichi Motoyama
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Correspondence to Naoki Yanagawa.

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Yanagawa, N., Osakabe, M., Hayashi, M. et al. Frequent epigenetic silencing of the FHIT gene in penile squamous cell carcinomas. Virchows Arch 452, 377–382 (2008). https://doi.org/10.1007/s00428-008-0597-6

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  • DOI: https://doi.org/10.1007/s00428-008-0597-6

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