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

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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

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Melanoma-Specific Antigens
Biomarkers
Neoplasm Metastasis
Neoplasms
Gene Expression Profiling
Uveal melanoma
Precision Medicine
Messenger RNA
Single Nucleotide Polymorphism
Research Design
Chromosomes
Mutation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Field, M. G., Decatur, C. L., Kurtenbach, S., Gezgin, G., Van Der Velden, P. A., Jager, M. J., ... William Harbour, J. (2016). PRAME as an independent biomarker for metastasis in uveal melanoma. Clinical Cancer Research, 22(5), 1234-1242. https://doi.org/10.1158/1078-0432.CCR-15-2071

PRAME as an independent biomarker for metastasis in uveal melanoma. / Field, Matthew G.; Decatur, Christina L.; Kurtenbach, Stefan; Gezgin, Gülçin; Van Der Velden, Pieter A.; Jager, Martine J.; Kozak, Kaleigh N.; William Harbour, J.

In: Clinical Cancer Research, Vol. 22, No. 5, 01.03.2016, p. 1234-1242.

Research output: Contribution to journalArticle

Field, MG, Decatur, CL, Kurtenbach, S, Gezgin, G, Van Der Velden, PA, Jager, MJ, Kozak, KN & William Harbour, J 2016, 'PRAME as an independent biomarker for metastasis in uveal melanoma', Clinical Cancer Research, vol. 22, no. 5, pp. 1234-1242. https://doi.org/10.1158/1078-0432.CCR-15-2071
Field MG, Decatur CL, Kurtenbach S, Gezgin G, Van Der Velden PA, Jager MJ et al. PRAME as an independent biomarker for metastasis in uveal melanoma. Clinical Cancer Research. 2016 Mar 1;22(5):1234-1242. https://doi.org/10.1158/1078-0432.CCR-15-2071
Field, Matthew G. ; Decatur, Christina L. ; Kurtenbach, Stefan ; Gezgin, Gülçin ; Van Der Velden, Pieter A. ; Jager, Martine J. ; Kozak, Kaleigh N. ; William Harbour, J. / PRAME as an independent biomarker for metastasis in uveal melanoma. In: Clinical Cancer Research. 2016 ; Vol. 22, No. 5. pp. 1234-1242.
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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.",
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T1 - PRAME as an independent biomarker for metastasis in uveal melanoma

AU - Field, Matthew G.

AU - Decatur, Christina L.

AU - Kurtenbach, Stefan

AU - Gezgin, Gülçin

AU - Van Der Velden, Pieter A.

AU - Jager, Martine J.

AU - Kozak, Kaleigh N.

AU - William Harbour, J.

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N2 - 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.

AB - 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.

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