COMPREHENSIVE MOLECULAR PROFILING OF UVEAL MELANOMA EVALUATED WITH GENE EXPRESSION PROFILING, PREFERENTIALLY EXPRESSED ANTIGEN IN MELANOMA EXPRESSION, AND NEXT-GENERATION SEQUENCING.

Abstract

Purpose: To determine the association between gene-expression profiling (GEP), next-generation sequencing (NGS), preferentially expressed antigen in melanoma (PRAME) features, and metastatic risk in patients with uveal melanoma (UM).

Methods: A retrospective analysis of patients with UM treated by brachytherapy or enucleation by a single ocular oncologist was conducted from November 2020 and July 2022. Clinicopathologic features, patient outcomes, GEP classification, NGS, and PRAME results were recorded.

Results: Comprehensive GEP, PRAME, and NGS testing was performed on 135 UMs. The presence of eukaryotic translation initiation factor 1A, X-chromosomal and splicing factor 3B subunit 1 mutations was significantly associated with GEP class 1A and GEP class 1B, respectively. The presence of BRCA- associated protein-1 mutation was significantly associated with GEP class 2. The average largest basal diameter for tumors with eukaryotic translation initiation factor 1A, X-chromosomal mutations was significantly smaller than those with splicing factor 3B subunit 1 mutations and BRCA1-associated protein-1 mutations. Class 2 tumors metastasized sooner than GEP class 1 tumors. Tumors with splicing factor 3B subunit 1 and/or BRCA1-associated protein-1 mutations metastasized sooner compared with tumors that had either no driver mutation or no mutations at all. Tumors with splicing factor 3B subunit 1 did not have a significantly different time to metastasis compared with tumors with BRCA1-associated protein-1 (P value = 0.97). Forty tumors (30%) were PRAME positive, and the remaining 95 tumors (70%) were PRAME negative. Tumors with PRAME-positive status did not have a significantly different time to metastasis compared with tumors without PRAME-positive status (P value = 0.11).

Conclusion: GEP, NGS, and PRAME expression analysis help determine different levels of metastatic risk in UM. Although other prognostic tests exist, the following study reports on the use of NGS for metastatic prognostication in UM. However, limitations of NGS exist, especially with small lesions that are technically difficult to biopsy.