scholarly journals GNAQ and PMS1 Mutations Associated with Uveal Melanoma, Ocular Surface Melanosis, and Nevus of Ota

2019 ◽  
Vol 5 (4) ◽  
pp. 267-272 ◽  
Author(s):  
Christopher B. Toomey ◽  
Kyle Fraser ◽  
John A. Thorson ◽  
Michael H. Goldbaum ◽  
Jonathan H. Lin
Keyword(s):  
G Protein ◽  
Uveal Melanoma ◽  
Ocular Surface ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Nevus Of Ota ◽  
Monosomy 3 ◽  
Target Amino Acid ◽  
Generation Sequencing ◽  
Uveal Melanomas

G protein mutations are common in uveal melanomas, and the vast majority target amino acid residue Q209 in either GNAQ or GNA11. The GNAQ R183Q mutation is found in a small fraction of uveal melanomas. We report a patient with an unusual presentation of uveal melanoma arising at an early age in the setting of congenital skin and ocular surface melanosis. A 34-year-old Hispanic female with congenital bilateral nevus of Ota and ocular surface melanosis presented with progressive loss of visual acuity and was found to have a juxtapapillary uveal melanoma. She was treated with brachytherapy, but the tumor relapsed. She underwent enucleation that revealed mixed spindle and epithelioid uveal melanoma cells with no extraocular or lymphovascular spread. Next-generation sequencing performed on DNA isolated from the enucleation specimen identified a GNAQ R183Q mutation and a PMS1 truncation mutation. Cytogenetic profiling revealed no monosomy 3. These findings raise the possibility that uveal melanomas bearing G protein R183 mutations may have distinct clinicopathologic profiles compared to those with Q209 mutations. Furthermore, this is the first reported case of a mutation in the mismatch repair gene PMS1 associated with uveal melanoma.

PREVALENCE OF MISMATCH REPAIR GENE MUTATIONS IN UVEAL MELANOMA

Retina ◽  
2020 ◽  
Vol 40 (11) ◽  
pp. 2216-2220
Author(s):  
Christopher B. Toomey ◽  
Nicholas J. Protopsaltis ◽  
Samantha Phou ◽  
Mathieu F. Bakhoum ◽  
John A. Thorson ◽  
...  
Keyword(s):  
Mismatch Repair ◽  
Uveal Melanoma ◽  
Gene Mutations ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Mismatch Repair Gene Mutations

scholarly journals Prognostic Values of G-Protein Mutations in Metastatic Uveal Melanoma

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5749
Author(s):  
Mizue Terai ◽  
Ayako Shimada ◽  
Inna Chervoneva ◽  
Liam Hulse ◽  
Meggie Danielson ◽  
...  
Keyword(s):  
G Protein ◽  
Uveal Melanoma ◽  
Gene Mutations ◽  
Driver Mutations ◽  
Protein Subunit ◽  
Metastatic Lesions ◽  
Impact On Survival ◽  
The Difference ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Uveal melanoma is the most common primary ocular malignancy in adults, characterized by gene mutations in G protein subunit alpha q (GNAQ) and G protein subunit alpha 11 (GNA11). Although they are considered to be driver mutations, their role in MUM remains elusive. We investigated key somatic mutations of MUM and their impact on patients’ survival after development of systemic metastasis (Met-to-Death). Metastatic lesions from 87 MUM patients were analyzed by next generation sequencing (NGS). GNA11 (41/87) and GNAQ (39/87) mutations were most predominantly seen in MUM. Most GNA11 mutations were Q209L (36/41), whereas GNAQ mutations comprised Q209L (14/39) and Q209P (21/39). Epigenetic pathway mutations BAP1 (42/66), SF3B1 (11/66), FBXW7 (2/87), PBRM1 (1/66), and SETD2 (1/66) were found. No specimen had the EIF1AX mutation. Interestingly, Met-to-Death was longer in patients with GNAQ Q209P compared to GNAQ/GNA11 Q209L mutations, suggesting the difference in mutation type in GNAQ/GNA11 might determine the prognosis of MUM. Structural alterations of the GNAQ/GNA11 protein and their impact on survival of MUM patients should be further investigated.

scholarly journals Digital morphometry of tumor nuclei correlates to BAP-1 status, monosomy 3, gene expression class and survival in uveal melanoma

2020 ◽  
Vol 193 ◽  
pp. 107987
Author(s):  
Christina Herrspiegel ◽  
Thonnie Rose O. See ◽  
Pia R. Mendoza ◽  
Hans E. Grossniklaus ◽  
Gustav Stålhammar
Keyword(s):  
Gene Expression ◽  
Uveal Melanoma ◽  
Monosomy 3

Hypothesis: Possible role of retinoic acid therapy in patients with biallelic mismatch repair gene defects

2007 ◽  
Vol 167 (2) ◽  
pp. 225-229 ◽  
Author(s):  
Sven Gottschling ◽  
Harald Reinhard ◽  
Constanze Pagenstecher ◽  
Stefan Krüger ◽  
Jochen Raedle ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Mismatch Repair ◽  
Mismatch Repair Gene ◽  
Repair Gene ◽  
Acid Therapy ◽  
Gene Defects

scholarly journals Small High-Risk Uveal Melanomas Have a Lower Mortality Rate

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2267
Author(s):  
Rumana N. Hussain ◽  
Sarah E. Coupland ◽  
Helen Kalirai ◽  
Azzam F. G. Taktak ◽  
Antonio Eleuteri ◽  
...  
Keyword(s):  
High Risk ◽  
Lead Time ◽  
Absolute Risk ◽  
Hazard Rates ◽  
Watch And Wait ◽  
Tumor Group ◽  
Monosomy 3 ◽  
The Difference ◽  
Oncology Centre ◽  
Uveal Melanomas

Our aim was to determine whether size impacts on the difference in metastatic mortality of genetically high-risk (monosomy 3) uveal melanomas (UM). We undertook a retrospective analysis of data from a patient cohort with genetically characterized UM. All patients treated for UM in the Liverpool Ocular Oncology Centre between 2007 and 2014, who had a prognostic genetic tumor analysis. Patients were subdivided into those with small (≤2.5 mm thickness) and large (>2.5 mm thickness) tumors. Survival analyses were performed using Gray rank statistics to calculate absolute probabilities of dying as a result of metastatic UM. The 5-year absolute risk of metastatic mortality of those with small monosomy 3 UM was significantly lower (23%) compared to the larger tumor group (50%) (p = 0.003). Small disomy 3 UM also had a lower absolute risk of metastatic mortality (0.8%) than large disomy 3 UM (6.4%) (p = 0.007). Hazard rates showed similar differences even with lead time bias correction estimates. We therefore conclude that earlier treatment of all small UM, particularly monosomy 3 UM, reduces the risk of metastatic disease and death. Our results would support molecular studies of even small UM, rather than ‘watch-and-wait strategies’.

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