An accurate, clinically feasible multi-gene expression assay for predicting metastasis in uveal melanoma

Michael D. Onken, Lori A. Worley, Meghan D. Tuscan, J. William Harbour

Research output: Contribution to journalArticle

185 Citations (Scopus)

Abstract

Uveal (ocular) melanoma is an aggressive cancer that often forms undetectable micrometastases before diagnosis of the primary tumor. These micrometastases later multiply to generate metastatic tumors that are resistant to therapy and are uniformly fatal. We have previously identified a gene expression profile derived from the primary tumor that is extremely accurate for identifying patients at high risk of metastatic disease. Development of a practical clinically feasible platform for analyzing this expression profile would benefit high-risk patients through intensified metastatic surveillance, earlier intervention for metastasis, and stratification for entry into clinical trials of adjuvant therapy. Here, we migrate the expression profile from a hybridization-based microarray platform to a robust, clinically practical, PCR-based 15-gene assay comprising 12 discriminating genes and three endogenous control genes. We analyze the technical performance of the assay in a prospective study of 609 tumor samples, including 421 samples sent from distant locations. We show that the assay can be performed accurately on fine needle aspirate biopsy samples, even when the quantity of RNA is below detectable limits. Preliminary outcome data from the prospective study affirm the prognostic accuracy of the assay. This prognostic assay provides an important addition to the armamentarium for managing patients with uveal melanoma, and it provides a proof of principle for the development of similar assays for other cancers.

Original languageEnglish
Pages (from-to)461-468
Number of pages8
JournalJournal of Molecular Diagnostics
Volume12
Issue number4
DOIs
StatePublished - Jul 1 2010
Externally publishedYes

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Neoplasm Metastasis
Gene Expression
Neoplasms
Neoplasm Micrometastasis
Prospective Studies
Genes
Fine Needle Biopsy
Transcriptome
Uveal melanoma
Clinical Trials
RNA
Polymerase Chain Reaction
Therapeutics

ASJC Scopus subject areas

  • Molecular Medicine
  • Pathology and Forensic Medicine

Cite this

An accurate, clinically feasible multi-gene expression assay for predicting metastasis in uveal melanoma. / Onken, Michael D.; Worley, Lori A.; Tuscan, Meghan D.; William Harbour, J.

In: Journal of Molecular Diagnostics, Vol. 12, No. 4, 01.07.2010, p. 461-468.

Research output: Contribution to journalArticle

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