Abstract
Purpose :
In uveal melanoma (UM), molecular prognostic testing using the prospectively validated 15-gene expression profile (GEP) test has been widely adopted in the US to guide risk-stratified treatment plans. The 15-GEP stratifies tumors according to their biological risk of metastasis as Class 1A (low risk), Class 1B (intermediate risk), or Class 2 (high risk). Tests for additional UM-associated biomarkers can now be simultaneously performed from the same biopsy specimen that is used for 15-GEP testing, including PRAME testing and next-generation sequencing (NGS) analysis with a custom 7-gene UM-targeted panel. This study describes the combined technical performance of all three tests, which together provide a comprehensive molecular tumor profile to enable highly individualized patient care.
Methods :
UM samples submitted for routine comprehensive clinical testing with all three tests (15-GEP, PRAME, and NGS) between February 2018 and October 2022 were anonymized and analyzed through an Institutional Review Board-exempt protocol.
Results :
Comprehensive 15-GEP, PRAME, and NGS testing was performed on 1996 tumors. One or more test results were successfully reported for ≥ 97.2% of specimens. In total, 87 samples (4.4%) had one or more test failures and were excluded from this analysis, resulting in 1909 cases with successful 15-GEP, PRAME, and NGS results. Testing with the 15-GEP resulted in 908 (47.6%) Class 1A, 347 (18.2%) Class 1B, and 654 (34.3%) Class 2 tumors. PRAME expression was positive in 526 (27.6%) tumors, including 19.0% of Class 1 (238/1255) and 44.0% of Class 2 (288/654) cases. Clinically reportable mutations were identified in GNA11 (817/1909, 42.8%), GNAQ (821, 43.0%), CYSLTR2 (12, 0.6%), PLCB4 (41, 2.1%), BAP1 (567, 29.7%), SF3B1 (224, 11.7%), and EIF1AX (372, 19.5%). Multiple genes were mutated in 1090 tumors (57.1%). No clinically significant mutations were identified in 299 cases (15.7%).
Conclusions :
This suite of clinically available molecular tests, performed via tandem RNA and genomic DNA extraction from a single UM biopsy sample, successfully produces results for the vast majority of submitted specimens. The tests are unique in providing comprehensive information from three distinct biomarker panels to better inform patient management decisions.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.