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Fragile genes as biomarkers: epigenetic control of WWOX and FHIT in lung, breast and bladder cancer

Oncogene volume 24, pages 1625–1633 (2005)Cite this article

Abstract

This study aimed to (a) determine if DNA methylation is a mechanism of WWOX (WW domain containing oxidoreductase) and FHIT (fragile histidine triad) inactivation in lung, breast and bladder cancers; (b) examine distinct methylation patterns in neoplastic and adjacent tissues and (c) seek correlation of methylation patterns with disease status. Protein expression was detected by immunohistochemistry, and methylation status by methylation-specific PCR (MSP) and sequencing, in lung squamous cell carcinomas and adjacent tissues, invasive breast carcinomas, adjacent tissues and normal mammary tissues and bladder transitional cell carcinomas. Wwox and Fhit expression was reduced in cancers in association with hypermethylation. Differential patterns of WWOX and FHIT methylation were observed in neoplastic vs adjacent non-neoplastic tissues, suggesting that targeted MSP amplification could be useful in following treatment or prevention protocols. WWOX promoter MSP differentiates DNA of lung cancer from DNA of adjacent lung tissue. WWOX and FHIT promoter methylation is detected in tissue adjacent to breast cancer and WWOX exon 1 MSP distinguishes breast cancer DNA from DNA of adjacent and normal tissue. Differential methylation in cancerous vs adjacent tissues suggests that WWOX and FHIT hypermethylation analyses could enrich a panel of DNA methylation markers.

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Acknowledgements

This work was supported by USPHS grants CA77738, CA56036 and training grant T32-HLO7780 (KAM); also supported by NIH contracts N01-CN-15128 and N01-CN-15113.

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Author notes

  1. Dimitrios Iliopoulos, Teresa Druck, Kelly A McCorkell & Kay Huebner

    Present address: Ohio State Comprehensive Cancer Center, 410W. 12th Ave, Rm 463 Wiseman Hall, Columbus, OH, 43210, USA

Authors and Affiliations

  1. Department of Microbiology-Immunology, Philadelphia, PA, 19107, USA

    Dimitrios Iliopoulos, Gulnur Guler, Shuang-Yin Han, Danika Johnston, Teresa Druck, Kelly A McCorkell & Kay Huebner

  2. Department of Pathology, Philadelphia, PA, 19107, USA

    Juan Palazzo & Peter A McCue

  3. Department of Urology, Kimmel Cancer Center, Philadelphia, PA, 19107, USA

    Raffaele Baffa

  4. Department of Pathology, Hacettepe University, Ankara, Turkey

    Gulnur Guler

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  1. Dimitrios Iliopoulos
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Correspondence to Kay Huebner.

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Iliopoulos, D., Guler, G., Han, SY. et al. Fragile genes as biomarkers: epigenetic control of WWOX and FHIT in lung, breast and bladder cancer. Oncogene 24, 1625–1633 (2005). https://doi.org/10.1038/sj.onc.1208398

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