Abstract
<div>Abstract<p><b>Purpose:</b> 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.</p><p><b>Experimental Design:</b> 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 tumors were further analyzed using global GEP and single nucleotide polymorphism microarrays. <i>PRAME</i> (preferentially expressed antigen in melanoma) mRNA expression was analyzed in 64 Class 1 tumors by qPCR.</p><p><b>Results:</b> Among Class 1 UMs, the most significant predictor of metastasis was <i>PRAME</i> mRNA expression (<i>P</i> = 0.0006). The 5-year actuarial rate of metastasis was 0% for Class1<sup>PRAME−</sup>, 38% for Class1<sup>PRAME+</sup>, and 71% for Class 2 tumors. Median metastasis-free survival for Class1<sup>PRAME+</sup> 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 Class1<sup>PRAME+</sup> tumors included gain of 1q, 6p, 8q, and 9q and loss of 6q and 11q. <i>PRAME</i> expression was associated with larger tumor diameter (<i>P</i> = 0.05) and <i>SF3B1</i> mutations (<i>P</i> = 0.003).</p><p><b>Conclusions:</b> <i>PRAME</i> 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. <i>Clin Cancer Res; 22(5); 1234–42. ©2016 AACR</i>.</p></div>
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callSimilar Papers
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
