Related Experiment Video
Updated: Oct 2, 2025
Comparative Lesions Analysis Through a Targeted Sequencing Approach
Published on: November 5, 2019
Genomic Profiling of Metastatic Uveal Melanoma Shows Frequent Coexisting BAP1 or SF3B1 and GNAQ/GNA11 Mutations and
Alexandra L Isaacson1, Ramakrishna R Sompallae1, Natalya V Guseva1
1Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA.
Objectives:
To identify therapeutic targets and correlate with clinical outcomes from mutation profiling of metastatic uveal melanoma (UM) using next-generation sequencing (NGS).
Methods:
Melanoma cases that were tested using DNA-based NGS panels of 25 and/or 214 genes were evaluated retrospectively (263 cases) and identified 27 UM cases. BAP1 expression was examined by immunohistochemistry.
Results:
Mutations in GNA11 (14) and GNAQ (12) were found in 96% (n = 27) of cases of UM, and most had coexisting BAP1 (17) or SF3B1 (4) mutations. Coexisting GNAQ/11-SF3B1 mutations correlated with a longer average time to first metastasis compared with GNAQ/11-BAP1 mutations (99.7 vs 38.5 months, P = .047). Three patients with BAP1 mutations received trametinib; two are still alive (15 months; 23 months), and one died (32 months). In non-UMs, only 4.2% (n = 236) had BAP1 and 3.8% had SF3B1 mutations; none had coexisting GNAQ/11 mutations.
Conclusions:
Coexisting BAP1/SF3B1 and GNAQ/11 mutations were unique to UM. SF3B1 mutations were reported to be UM-specific in melanoma and associated with rare/no metastasis. The finding of mutated SF3B1 in 14.8% (n = 27) of UMs suggests its role should be further evaluated. The correlation of BAP1/SF3B1 mutation with survival also warrants investigation.
