The Genetics of Uveal Melanoma: Overview and Clinical Relevance

2021 ◽  
Vol 238 (07) ◽  
pp. 773-780
Author(s):  
Aline Isabel Riechardt ◽  
Emine Kilic ◽  
Antonia M. Joussen
Keyword(s):  
Genetic Counselling ◽  
Uveal Melanoma ◽  
Chromosomal Aberrations ◽  
Clinical Relevance ◽  
Genetic Evolution ◽  
Genetic Characteristics ◽  
Mutational Burden ◽  
Genetic Subtype ◽  
Monosomy 3 ◽  
Work Up

AbstractOver the last ten years, much has been learnt about the genetic characteristics and genetic evolution of uveal melanoma. It has been shown that uveal melanoma differs fundamentally from non-uveal melanoma and is an independent genetic subtype. Compared to other tumours, uveal melanoma has a low mutational burden. There are recurring chromosomal aberrations with losses of 1p, 6q, 8p and 16q, gains of 6p and 8q, and the presence of monosomy 3. GNAQ, GNA11, PLCB4, CYSLTR2, MAPKAPK5, as well as mutations in BAP1, SF3B1, SRSF2 and EIF1AX, the latter being linked to a higher risk of metastasis, have been identified as significantly mutated genes. In rare cases, a BAP1 germline mutation may also be present. In addition to higher risk of uveal melanoma, this variant is also linked with other tumours. In this case, additional work-up, genetic counselling and screening of family members should be offered. While the knowledge about the genetic characteristics of uveal melanoma is already routinely used for diagnostic and prognostic purposes, targeted genotype-dependent therapy of uveal melanoma is currently still missing.

scholarly journals Clinico-Pathological Association of Delineated miRNAs in Uveal Melanoma with Monosomy 3/Disomy 3 Chromosomal Aberrations

PLoS ONE ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. e0146128 ◽  
Author(s):  
Nalini Venkatesan ◽  
Jagat Kanwar ◽  
Perinkulam Ravi Deepa ◽  
Vikas Khetan ◽  
Tamsyn M. Crowley ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Chromosomal Aberrations ◽  
Monosomy 3

scholarly journals Multiregional genetic evolution of metastatic uveal melanoma

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Daniel A. Rodriguez ◽  
Jessica Yang ◽  
Michael A. Durante ◽  
Alexander N. Shoushtari ◽  
Stergios J. Moschos ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Tumor Development ◽  
Genetic Evolution ◽  
Metastatic Progression ◽  
Therapeutic Approaches ◽  
Primary Tumors ◽  
Early Tumor ◽  
Rapid Autopsy ◽  
Genetic Events ◽  
Novel Therapeutic

AbstractUveal melanoma (UM) is the most common primary intraocular malignancy in adults and leads to deadly metastases for which there is no approved treatment. Genetic events driving early tumor development are well-described, but those occurring later during metastatic progression remain poorly understood. We performed multiregional genomic sequencing on 22 tumors collected from two patients with widely metastatic UM who underwent rapid autopsy. We observed multiple seeding events from the primary tumors, metastasis-to-metastasis seeding, polyclonal seeding, and late driver variants in ATM, KRAS, and other genes previously unreported in UM. These findings reveal previously unrecognized temporal and anatomic complexity in the genetic evolution of metastatic uveal melanoma, and they highlight the distinction between early and late phases of UM genetic evolution with implications for novel therapeutic approaches.

Role of somatic mutations and chromosomal aberrations in the prognosis of uveal melanoma in a Spanish patient cohort

2021 ◽  
Author(s):  
Paula Silva‐Rodríguez ◽  
Manuel Bande ◽  
Daniel Fernández‐Díaz ◽  
Nerea Lago‐Baameiro ◽  
María Pardo ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Chromosomal Aberrations ◽  
Somatic Mutations ◽  
Spanish Patient ◽  
Patient Cohort

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

scholarly journals Origin and clinical relevance of chromosomal aberrations other than the common trisomies detected by genome-wide NIPS: results of the TRIDENT study

2017 ◽  
Vol 20 (5) ◽  
pp. 480-485 ◽  
Author(s):  
Diane Van Opstal ◽  
◽  
Merel C van Maarle ◽  
Klaske Lichtenbelt ◽  
Marjan M Weiss ◽  
...  
Keyword(s):  
Chromosomal Aberrations ◽  
Clinical Relevance ◽  
Genome Wide ◽  
The Common

Diagnosis of blue nevus-like metastatic uveal melanoma confirmed by fluorescence in situ hybridization (FISH) for monosomy 3

2012 ◽  
Vol 39 (6) ◽  
pp. 621-625 ◽  
Author(s):  
Klaus J. Busam ◽  
Yuqiang Fang ◽  
Suresh Jhanwar ◽  
Mario Lacouture
Keyword(s):  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Uveal Melanoma ◽  
Blue Nevus ◽  
Monosomy 3

scholarly journals Audit of the Aetiological Investigations Performed in Children with Sensorineural Hearing Loss At Salford

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Saud K AlHajeri ◽  
Dr Mohammed Iqbal
Keyword(s):  
Hearing Loss ◽  
Genetic Testing ◽  
Sensorineural Hearing Loss ◽  
Genetic Counselling ◽  
Gold Standard ◽  
Sensorineural Hearing ◽  
British Association ◽  
Hearing Tests ◽  
Work Up

Objective: This project aims to look at the Audiovestibular Physician’s practice at Salford and how closely it aligns with the gold standard guidelines set in the protocol lately published by the British Association of Audiological Physicians. Method: An audit was done retrospectively on 20 patients suffering from sensorineural hearing loss. As such, patient notes were utilised to ascertain which aetiological investigations have been completed and which were not. Any inadequacy in the aetiological work up has been dissected to help know the underlying reasons. Results: All patients had a thorough history taken and were comprehensively physically examined. 95% of patients underwent imaging in the form of MRI/CT. 80% received CMV testing. 75% underwent ECG testing. 60% received family hearing tests. Only 35% had ophthalmology examinations and 25% underwent urine and genetic testing. Conclusion: In some cases, the low compliance rates were due to the Audiovestibular Physician not ordering the investigation as part of the aetiological work up. This could be improved with the use of a dedicated checklist to act as an aid to the physician. Moreover, genetic counselling has been proposed to attempt to boost the compliance rates with genetic testing and similarly, leaflets briefing patients’ families about the importance of undergoing hearing tests themselves is another promising proposition to help improve the adherence

scholarly journals Metabolic activity of primary uveal melanoma on PET/CT scan and its relationship with monosomy 3 and other prognostic factors

2014 ◽  
Vol 98 (12) ◽  
pp. 1659-1665 ◽  
Author(s):  
Vasilios P Papastefanou ◽  
Shahriar Islam ◽  
Teresa Szyszko ◽  
Marianne Grantham ◽  
Mandeep S Sagoo ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Ct Scan ◽  
Uveal Melanoma ◽  
Metabolic Activity ◽  
Pet Ct ◽  
Monosomy 3 ◽  
Pet Ct Scan

The Heterogeneous Distribution of Monosomy 3 in Uveal Melanomas: Implications for Prognostication Based on Fine-Needle Aspiration Biopsies

2007 ◽  
Vol 131 (1) ◽  
pp. 91-96 ◽  
Author(s):  
Willem Maat ◽  
Ekaterina S. Jordanova ◽  
Shama L. van Zelderen-Bhola ◽  
Ed R. Barthen ◽  
Hans W. Wessels ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Fine Needle Aspiration ◽  
Fine Needle Aspiration Biopsy ◽  
Needle Aspiration ◽  
Chromosome 3 ◽  
Fish Analysis ◽  
Paraffin Sections ◽  
Heterogeneous Distribution ◽  
Fine Needle ◽  
Monosomy 3

Abstract Context.—The detection of monosomy 3 in uveal melanomas has repeatedly been associated with adverse outcome. Fine-needle aspiration biopsy is being used to detect monosomy 3 in these tumors, based on the assumption that this chromosomal abnormality is distributed homogeneously throughout the tumor. Objective.—To study the distribution of monosomy 3 in primary uveal melanoma by fluorescence in situ hybridization (FISH). Design.—We studied 50 enucleated eyes with uveal melanoma. In all 50 tumors we performed cytogenetic analysis and FISH using a DNA-specific probe for the centromere region of chromosome 3 on cultured tumor cells. In addition, the percentage of tumor cells with monosomy 3 was assessed by FISH on nuclei, isolated from paraffin-embedded tissue and compared to results of FISH on regular histology sections of the paraffin-embedded tissue. Results.—Combining karyotyping and FISH on cultured cells identified monosomy 3 in 19 (38%) of 50 tumors, whereas FISH on nuclei isolated from paraffin-embedded tissue showed 31 (62%) of 50 as having monosomy for chromosome 3. FISH analysis on paraffin sections showed tumor heterogeneity for copy number of chromosome 3 in at least 7 cases. Conclusions.—FISH analysis on paraffin sections shows that heterogeneity of monosomy of chromosome 3 is a frequent phenomenon in uveal melanoma. FISH on nuclei isolated from paraffin-embedded tissue identifies a higher frequency of monosomy 3 than the traditional combination of karyotyping and FISH on cultured uveal melanoma cells. The practice of assigning patients to risk categories based on fine-needle aspiration biopsy samples from primary uveal melanoma may be subject to error based on the heterogeneous distribution of monosomy 3 in these tumors.

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.

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