期刊
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
卷 158, 期 2, 页码 177-186出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/ajcp/aqac019
关键词
Uveal melanoma; Genomic profiling; BAP1
类别
资金
- Department of Pathology at University of Iowa Hospitals and Clinics
This study aimed to identify therapeutic targets and correlate with clinical outcomes in metastatic UM through mutation profiling using NGS. The results showed that GNAQ/11-SF3B1 mutations were associated with a longer time to first metastasis compared to GNAQ/11-BAP1 mutations. Coexisting BAP1/SF3B1 and GNAQ/11 mutations were unique to UM, and SF3B1 mutations may play a role in UM metastasis.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据