title: EDD, the human orthologue of the hyperplastic discs tumour suppressor gene, is amplified and overexpressed in cancer.
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.
authors.affiliation: Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria St., Darlinghurst, NSW 2010, Australia.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Clancy
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Henderson
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Russell
authors.forename: David W
authors.initials: DW
authors.lastname: Anderson
authors.forename: Ronaldo J
authors.initials: RJ
authors.lastname: Bova
authors.forename: Ian G
authors.initials: IG
authors.lastname: Campbell
authors.forename: David Y H
authors.initials: DY
authors.lastname: Choong
authors.forename: Graeme A
authors.initials: GA
authors.lastname: Macdonald
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Mann
authors.forename: Tania
authors.initials: T
authors.lastname: Nolan
authors.forename: Ged
authors.initials: G
authors.lastname: Brady
authors.forename: Olufunmilayo I
authors.initials: OI
authors.lastname: Olopade
authors.forename: Erica
authors.initials: E
authors.lastname: Woollatt
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Davies
authors.forename: Davendra
authors.initials: D
authors.lastname: Segara
authors.forename: Neville F
authors.initials: NF
authors.lastname: Hacker
authors.forename: Susan M
authors.initials: SM
authors.lastname: Henshall
authors.forename: Robert L
authors.initials: RL
authors.lastname: Sutherland
authors.forename: Colin K W
authors.initials: CK
authors.lastname: Watts
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D002869:Chromosome Aberrations; D002898:Chromosomes, Human, Pair 8; D005260:Female; D006801:Humans; D018895:Microsatellite Repeats; D009369:Neoplasms / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics*; D010453:Peptide Synthases / Q000096:biosynthesis / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases
chemical_list: C117617:UBR5 protein, human; D044767:Ubiquitin-Protein Ligases; D010453:Peptide Synthases