PRAME as an independent biomarker for metastasis in uveal melanoma

Matthew G. Field, Christina L. Decatur, Stefan Kurtenbach, Gülçin Gezgin, Pieter A. Van Der Velden, Martine J. Jager, Kaleigh N. Kozak, J. William Harbour

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

Purpose: Uveal melanoma (UM) can be classified by gene expression profiling (GEP) into Class 1 (low metastatic risk) and Class 2 (high metastatic risk), the latter being strongly associated with mutational inactivation of the tumor suppressor BAP1. Nevertheless, a small percentage of Class 1 tumors give rise to metastatic disease. The purpose of this study was to identify biomarkers of metastasis in Class 1 tumors. Experimental Design: A total of 389 consecutive patients with UM were assigned to Class 1 or Class 2 using a prospectively validated 12-gene prognostic classifier. Selected tumorswere further analyzed using global GEP and single nucleotide polymorphism microarrays. PRAME (preferentially expressed antigen in melanoma) mRNA expression was analyzed in 64 Class 1 tumors by qPCR. Results: Among Class 1 UMs, the most significant predictor of metastasis was PRAME mRNA expression (P = 0.0006). The 5-year actuarial rate of metastasis was0%for Class1PRAME-, 38% for Class1PRAME+, and 71% for Class 2 tumors. Median metastasisfree survival for Class1PRAME+ patients was 88 months, compared to 32 months for Class 2 patients. Findings were validated using three independent datasets, including one using disomy 3 to identify low-risk UM. Chromosome copy number changes associated with Class1PRAME+ tumors included gain of 1q, 6p, 8q, and 9q and loss of 6q and 11q. PRAME expression was associated with larger tumor diameter (P = 0.05) and SF3B1 mutations (P = 0.003). Conclusions: PRAME is an independent prognostic biomarker in UM, which identifies increased metastatic risk in patients with Class 1 or disomy 3 tumors. This finding may further enhance the accuracy of prognostic testing and precision medicine for UM. Clin Cancer Res; 22(5); 1234-42.

Original languageEnglish (US)
Pages (from-to)1234-1242
Number of pages9
JournalClinical Cancer Research
Volume22
Issue number5
DOIs
StatePublished - Mar 1 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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