Genomic Profiling of Metastatic Uveal Melanoma Shows Frequent Coexisting BAP1 or SF3B1 and GNAQ/GNA11 Mutations and Correlation With Prognosis

Alexandra L Isaacson; Ramakrishna R Sompallae; Natalya V Guseva; Andrew M Bellizzi; Aaron D Bossler; Deqin Ma

doi:10.1093/ajcp/aqac019

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Genomic Profiling of Metastatic Uveal Melanoma Shows Frequent Coexisting BAP1 or SF3B1 and GNAQ/GNA11 Mutations and Correlation With Prognosis

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Genomic Profiling of Metastatic Uveal Melanoma Shows Frequent Coexisting BAP1 or SF3B1 and GNAQ/GNA11 Mutations and Correlation With Prognosis

Alexandra L Isaacson, Ramakrishna R Sompallae, Natalya V Guseva, Andrew M Bellizzi, Aaron D Bossler and Deqin Ma

American journal of clinical pathology, Vol.158(2), pp.177-186

02/25/2022

DOI: 10.1093/ajcp/aqac019

PMID: 35212356

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Abstract

To identify therapeutic targets and correlate with clinical outcomes from mutation profiling of metastatic uveal melanoma (UM) using next-generation sequencing (NGS). 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. 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. 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.

Uveal melanoma

SF3B1

Genomic profiling

BAP1

Details

Title: Subtitle: Genomic Profiling of Metastatic Uveal Melanoma Shows Frequent Coexisting BAP1 or SF3B1 and GNAQ/GNA11 Mutations and Correlation With Prognosis
Creators: Alexandra L Isaacson - Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
Ramakrishna R Sompallae - Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
Natalya V Guseva - Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
Andrew M Bellizzi - Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
Aaron D Bossler - Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
Deqin Ma - Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: American journal of clinical pathology, Vol.158(2), pp.177-186
DOI: 10.1093/ajcp/aqac019
PMID: 35212356
NLM abbreviation: Am J Clin Pathol
eISSN: 1943-7722
Language: English
Electronic publication date: 02/25/2022
Academic Unit: Pathology
Record Identifier: 9984222807002771

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