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  • Oncogenomics
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EDD, the human orthologue of the hyperplastic discs tumour suppressor gene, is amplified and overexpressed in cancer

Oncogene volume 22, pages 5070–5081 (2003)Cite this article

Abstract

EDD (E3 isolated by differential display), located at chromosome 8q22.3, is the human orthologue of the Drosophila melanogaster tumour suppressor gene ‘hyperplastic discs’ and encodes a HECT domain E3 ubiquitin protein-ligase. To investigate the possible involvement of EDD in human cancer, several cancers from diverse tissue sites were analysed for allelic gain or loss (allelic imbalance, AI) at the EDD locus using an EDD-specific microsatellite, CEDD, and other polymorphic microsatellites mapped in the vicinity of the 8q22.3 locus. Of 143 cancers studied, 38 had AI at CEDD (42% of 90 informative cases). In 14 of these cases, discrete regions of imbalance encompassing 8q22.3 were present, while the remainder had more extensive 8q aberrations. AI of CEDD was most frequent in ovarian cancer (22/47 informative cases, 47%), particularly in the serous subtype (16/22, 73%), but was rare in benign and borderline ovarian tumours. AI was also common in breast cancer (31%), hepatocellular carcinoma (46%), squamous cell carcinoma of the tongue (50%) and metastatic melanoma (18%). AI is likely to represent amplification of the EDD gene locus rather than loss of heterozygosity, as quantitative RT–PCR and immunohistochemistry showed that EDD mRNA and protein are frequently overexpressed in breast and ovarian cancers, while among breast cancer cell lines EDD overexpression and increased gene copy number were correlated. These results demonstrate that AI at the EDD locus is common in a diversity of carcinomas and that the EDD gene is frequently overexpressed in breast and ovarian cancer, implying a potential role in cancer progression.

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Abbreviations

AI:

allelic imbalance

CA II:

carbonic anhydrase II

CEDD:

CA repeat within EDD

CGH:

comparative genomic hybridization

EDD:

E3 isolated by differential display

FISH:

fluorescence in situ hybridization

IHC:

immunohistochemistry

LOH:

loss of heterozygosity

MI:

microsatellite instability

p53R2:

p53 ribonucleotide reductase

SSCP:

single-stranded conformational polymorphism

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Acknowledgements

We thank Gillian Lehrbach, Saskia IJ Ellenbroek, Darren Saunders, Samantha Hird, and other members of the Cancer Research Program for technical assistance and helpful discussions and Nigel Bundred at the University of Manchester for the supply of clinical materials.

This work was supported by the National Health and Medical Research Council of Australia (NHMRC), the US Army Medical Research and Materiel Command Breast Cancer Research Program (Grants DAMD17-98-1-8335 and DAMD17-00-1-253), The Cancer Council New South Wales, the Association for International Cancer Research, the Gynaecological Oncology (GO) Fund of the Royal Hospital for Women Foundation Sydney, Australia and the RT Hall Trust.

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Authors and Affiliations

  1. Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Australia

    Jennifer L Clancy, Michelle J Henderson, Amanda J Russell, Ronaldo J Bova, Michael J Davies, Davendra Segara, Susan M Henshall, Robert L Sutherland & Colin KW Watts

  2. Laboratory of Molecular Genetics, NIDCD/NIH, Rockville, MD, USA

    David W Anderson

  3. Peter MacCallum Cancer Institute, Melbourne, Victoria, Australia

    Ian G Campbell & David YH Choong

  4. Population and Clinical Sciences Division, Queensland Institute of Medical Research and Department of Medicine, The University of Queensland, Brisbane, Australia

    Graeme A Macdonald

  5. Westmead Institute of Cancer Research, University of Sydney at Westmead Millennium Institute, Westmead, Australia

    Graham J Mann

  6. School of Biological Sciences, University of Manchester, Manchester, UK

    Tania Nolan & Ged Brady

  7. Center for Medical Genetics, University of Chicago Medical Center, Chicago, IL, USA

    Olufunmilayo I Olopade

  8. Center for Medical Genetics, Women's and Children's Hospital, Adelaide, Australia

    Erica Woollatt

  9. Gynaecological Cancer Centre, Royal Hospital for Women, Randwick, NSW 2031, Australia

    Neville F Hacker

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  1. Jennifer L Clancy
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Correspondence to Colin KW Watts.

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Clancy, J., Henderson, M., Russell, A. et al. EDD, the human orthologue of the hyperplastic discs tumour suppressor gene, is amplified and overexpressed in cancer. Oncogene 22, 5070–5081 (2003). https://doi.org/10.1038/sj.onc.1206775

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