The Role of Mutation Rates of GNAQ or GNA11 in Cases of Uveal Melanoma in Japan

Ominato, Jun; Fukuchi, Takeo; Sato, Ayako; Yamaguchi, Naoyuki; Kobayashi, Kazue; Cho, Hiroyuki; Oyama, Tokuhide; Ajioka, Yoichi

doi:10.1097/pai.0000000000000505

Cited by 7 publications

(13 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is unknown whether this is a result of inadequate study samples in previous research that limited the power of the statistical analysis. Ominato et al [34] found in 19 Japanese UM patients that the frequency of GNAQ and GNA11 was 57.9%. These mutation frequencies for GNAQ and GNA11 were obviously lower than ours although they were studied in an Asian population.…”

Section: Discussionmentioning

confidence: 99%

Mutations of GNAQ, GNA11, SF3B1, EIF1AX, PLCB4 and CYSLTR in Uveal Melanoma in Chinese Patients

et al. 2019

View full text Add to dashboard Cite

Background: The purpose of this study is to determine the mutation frequencies of key driver genes in uveal melanoma (UM) in Chinese patients and to detect associations between metastasis and the mutation of these genes. Method: A total of 85 patients with UM were enrolled in this study, including 18 patients with metastasis and 67 without metastasis. Sanger sequencing covering the mutational hotspot regions of the G protein subunit alpha Q (GNAQ), GNA11, splicing factor 3B subunit 1 (SF3B1), X-linked eukaryotic translation initiation factor 1A (EIF1AX), phospholipase C beta 4 (PLCB4) and cysteinyl leukotriene receptor 2 (CYSLTR2) genes was used to analyse the mutations in Chinese patients. Results: The frequencies of GNAQ and GNA11 mutations in UM were 45% (38/85) and 35% (30/85) respectively. The frequencies of SF3B1 and EIF1AX mutations were 37% (31/85) and 9% (8/85) respectively. Only 2 mutations were detected in exon 4 of GNAQ, and no mutations were detected in exon 4 of GNA11. A novel mutation, c.627G>T (Q209H) in GNA11 was found. The detected mutations affecting SF3B1 were c.1873C>T (R625C), c.1874G>A (R625H) and c.1874G>T (R625L). The association between the mutations in SF3B1 and low risk of metastasis was statistically significant (OR 0.17, 95% CI 0.035-0.819). The mutations affecting EIF1AX were -23G>A (5′-UTR), c.5C>G (P2R), c.23G>A (G8Q), c.25G>C (G9A) and c.38_39GC>CT (R13P). No mutations were found in the PLCB4 and CYSLTR2 genes. Unfortunately, information on BRCA1-associated protein 1 could not be obtained. Conclusions: These data indicate that mutations in the PLCB4 and CYSLTR2 genes are rare in Chinese UM patients. The mutations in GNAQ, GNA11 and EIF1AX were not associated with metastasis, whereas SF3B1 mutations were correlated with low risk of metastasis and demonstrated a protective effect in UM patients in China.

show abstract

Section: Discussionmentioning

confidence: 99%

Mutations of GNAQ, GNA11, SF3B1, EIF1AX, PLCB4 and CYSLTR in Uveal Melanoma in Chinese Patients

et al. 2019

View full text Add to dashboard Cite

show abstract

“…(2) The overall frequency of GNAQ/ GNA11 mutations in different populations is variable. Analyses of UM from Dutch, American, Japanese, Greek and Chinese populations reveal a frequency of GNAQ/GNA11 mutations of 93.4%, (23) 83.0%, (24) 57.9%, (25) 42.4% (26) and 38.0%, (27) respectively. The frequency of GNAQ/GNA11 mutations in the South Indian population has not been reported.…”

Section: Discussionmentioning

confidence: 99%

Clinical spectrum, treatment and outcomes of uveal melanoma in a tertiary centre

Wong

Sundar

Chee

et al. 2019

smedj

View full text Add to dashboard Cite

Uveal melanoma (UM) is an aggressive intraocular malignancy, and despite advances in the local methods of treatment of primary UM, the survival rates have not improved. (1) This is thought to be due to the tumour's proclivity for early occult micro-metastasis, which is undetectable at the time of diagnosis and treatment of the primary tumour. (2,3) At present, there are no effective chemotherapeutic agents for metastatic UM, (3) with death rates from melanoma-related metastasis at 80% at one year and 92% at two years. (4) The most common primary intraocular tumour in Caucasian adults is UM. The reported age-standardised incidence rate in the United States and Europe is 5.1 per million (5) and 2.6-7.5 per million, respectively. In contrast, the age-standardised incidence rate in South Korea and Japan is 0.6 per million (6) and 0.2 per million, (7) respectively. The literature on the clinicopathologic spectrum of UM is largely derived from a Western setting. In the Collaborative Ocular Melanoma Study (COMS), as well as a more recently published series of 8,100 patients with UM, 97%-98% of patients were Caucasian, with Asian patients representing < 1% of patients in both cohorts. (8,9) Aside from significant epidemiological heterogeneity, there is also marked biological diversity in UM. In recent years, the genetic abnormalities in UMs have been found to be distinct from those in cutaneous melanomas. In contrast to cutaneous melanomas, UMs lack mutations in B rapidly accelerated fibrosarcoma (BRAF), neuroblastoma rapidly accelerated sarcoma (NRAS) and Kit genes. (2,10) Instead, mutations in guanine nucleotide-binding protein subunit alpha-Q (GNAQ) and guanine nucleotide-binding protein subunit alpha-11 (GNA11) are early events in UM tumorigenesis. BRCA1 associated protein-1 (BAP1) is implicated in tumour progression and metastasis. (11) The cytogenetic profiles in UMs based on normal disomy 3, 6, 8, or partial/complete monosomy 3, 6p gain/loss, 6q gain/loss, 8p gain/loss, and 8p gain/loss have also been found to be predictive of the risk of melanoma-related metastasis. (12) Our study reports the clinical characteristics, treatment patterns and outcomes of patients with UM treated in a tertiary centre in Southeast Asia. METHODSPatients with a diagnosis of UM made by clinical and/or pathologic analysis and who were followed up in our centre between 2002 and 2017 were retrospectively reviewed. Information on the patients' baseline demographics, clinical presentation, treatment and survival outcomes was collected. Approval from our Institutional Review Board was obtained.Choroidal melanoma (CM) was classified as small, medium or large based on the criteria established by the COMS. A melanoma INTRODUCTION We aimed to describe the clinical characteristics, diagnostic challenges, treatment patterns and outcomes of uveal melanoma (UM) in a tertiary care centre.METHODS This is a retrospective case series of 11 consecutive patients with UM who were managed in a tertiary referral centre between 2002 and 2017. Epidemiological, ...

show abstract

“…In the scientific literature, the frequencies of GNAQ mutations have been reported to range from 24.2 to 53.3% and those of GNA11 mutations from 24.2 to 60% [20,[28][29][30][31]. In previous studies, non-Caucasian populations have shown reduced mutation frequencies in these two genes, but more recent studies have shown that mutations in this population may be closer to the frequencies previously mentioned [32,33]. This could indicate that ethnic and demographic variables could play important roles that are yet to be elucidated.…”

Section: Gna11 Genesmentioning

confidence: 72%

“…Mutational hotspots in both genes have already been described in the literature, characterised by the presence of activating missense variants that exclusively affect exons 4 and 5, and more specifically, the arginine 183 (R183) and glutamine 209 (Q209) codons. The majority of GNA11 mutations in codon 209 leads to glutamine to leucine (p.Q209L) and proline (p.Q209P) substitutions [20,29,32,34]. These mutations occur from one-base substitutions at codon 209 (CAG), with the most common substitutions of A > T (94.5%) and A > C (2.7%) [19].…”

Section: Gna11 Genesmentioning

confidence: 99%

GNAQ and GNA11 Genes: A Comprehensive Review on Oncogenesis, Prognosis and Therapeutic Opportunities in Uveal Melanoma

Silva-Rodríguez

Fernandez-Diaz

Bande

et al. 2022

Cancers

View full text Add to dashboard Cite

The GNAQ and GNA11 genes are mutated in almost 80–90% of uveal melanomas in a mutually exclusive pattern. These genes encode the alpha subunits of the heterotrimeric G proteins, Gq and G11; thus, mutations of these genes result in the activation of several important signaling pathways, including phospholipase C, and activation of the transcription factor YAP. It is well known that both of them act as driver genes in the oncogenic process and it has been assumed that they do not play a role in the prognosis of these tumours. However, it has been hypothesised that mutations in these genes could give rise to molecularly and clinically distinct types of uveal melanomas. It has also been questioned whether the type and location of mutation in the GNAQ and GNA11 genes may affect the progression of these tumours. All of these questions, except for their implications in carcinogenesis, remain controversial. Uveal melanoma has a distinctive genetic profile, and specific recurrent mutations, which make it a potential candidate for treatment with targeted therapy. Given that the most frequent mutations are those observed in the GNAQ and GNA11 genes, and that both genes are involved in oncogenesis, these molecules, as well as the downstream signalling pathways in which they are involved, have been proposed as promising potential therapeutic targets. Therefore, in this review, special attention is paid to the current data related to the possible prognostic implications of both genes from different perspectives, as well as the therapeutic options targeting them.

show abstract

The Role of Mutation Rates of GNAQ or GNA11 in Cases of Uveal Melanoma in Japan

Cited by 7 publications

References 22 publications

Mutations of GNAQ, GNA11, SF3B1, EIF1AX, PLCB4 and CYSLTR in Uveal Melanoma in Chinese Patients

Mutations of GNAQ, GNA11, SF3B1, EIF1AX, PLCB4 and CYSLTR in Uveal Melanoma in Chinese Patients

Clinical spectrum, treatment and outcomes of uveal melanoma in a tertiary centre

GNAQ and GNA11 Genes: A Comprehensive Review on Oncogenesis, Prognosis and Therapeutic Opportunities in Uveal Melanoma

Contact Info

Product

Resources

About