DDEF1 is located in an amplified region of chromosome 8q and is overexpressed in uveal melanoma

Justis P. Ehlers, Lori Worley, Michael D. Onken, J. William Harbour

Research output: Contribution to journalArticle

91 Citations (Scopus)

Abstract

Purpose: The molecular pathogenesis of uveal melanoma is poorly understood but is usually accompanied by amplification of chromosome 8q, suggesting the activation of one or more oncogenes. We recently identified a gene expression profile that distinguishes low-grade from high-grade melanomas. In this profile, a cluster of genes at chromosome 8q was overexpressed in high-grade tumors, providing an opportunity to search for potential oncogenes in this region. Experimental Design: Gene expression microarray analysis was done on 25 primary uveal melanomas. Microarray comparative genomic hybridization (CGH), quantitative PCR, and immunohistochemistry were done on a subset of these tumors. Cell motility was measured using a wound-healing assay. Results: In melanomas analyzed for microarray gene expression and CGH, gain of chromosome 8q correlated most strongly with expression of DDEF1, a gene located at 8q24. In contrast, the nearby MYC oncogene exhibited no significant change in expression. Confirming the microarray findings, DDEF1 mRNA levels and protein expression were significantly higher in high-grade melanomas. Furthermore, ectopic expression of DDEF1 in low-grade melanoma cells resulted in a significant increase in cell motility, a feature of high-grade metastasizing cells. Conclusions: These findings suggest that DDEF1 overexpression may be a pathogenetically relevant consequence of chromosome 8q amplification, which commonly occurs in high-grade uveal melanomas. We conclude that DDEF1 may act as an oncogene in this cancer, and it may be a useful diagnostic marker and therapeutic target.

Original languageEnglish
Pages (from-to)3609-3613
Number of pages5
JournalClinical Cancer Research
Volume11
Issue number10
DOIs
StatePublished - May 15 2005
Externally publishedYes

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Oncogenes
Melanoma
Chromosomes
Comparative Genomic Hybridization
Cell Movement
Gene Expression
Neoplasms
Microarray Analysis
Multigene Family
Transcriptome
Wound Healing
Research Design
Immunohistochemistry
Polymerase Chain Reaction
Messenger RNA
Uveal melanoma
Genes
Proteins
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

DDEF1 is located in an amplified region of chromosome 8q and is overexpressed in uveal melanoma. / Ehlers, Justis P.; Worley, Lori; Onken, Michael D.; William Harbour, J.

In: Clinical Cancer Research, Vol. 11, No. 10, 15.05.2005, p. 3609-3613.

Research output: Contribution to journalArticle

Ehlers, Justis P. ; Worley, Lori ; Onken, Michael D. ; William Harbour, J. / DDEF1 is located in an amplified region of chromosome 8q and is overexpressed in uveal melanoma. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 10. pp. 3609-3613.
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