The Role of Genetic Mutations and of Circulating mRNAs in Uveal Melanoma
Study Details
Study Description
Brief Summary
The aim of the study is to identify genetic and epigenetic biomarkers in uveal melanoma, and to evaluate their diagnostic and prognostic role.
In particular, the specific objectives are:
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to identify the circulating somatic mutations associated with uveal melanoma;
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to identify the de-regulated miRNAs associated with uveal melanoma;
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to evaluate the diagnostic and prognostic role of the identified genetic and epigenetic markers;
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to identify possible therapeutic targets.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
This is a prospective, multicentric, case-control study, aimed at studying the gene and epigenetic mechanisms involved in uveal melanoma.
Patients with uveal melanoma, will be enrolled. For each subject included in the study, in a blood sample will be searched the mutations of the GNA11 and GNAQ genes and the expression of the following microRNAs: miR - 506-514 cluster, hsamiR - 592 and hsa - miR - 199a - 5p; the digital PCR droplet system will be used.
The study will not change the diagnostic-therapeutic process adopted in the clinical practice and will have no influence on the clinical management of enrolled patients.
A group of age sex matched controls will be recruited among patients scheduled for cataract surgery.
The sample size was calculated to detect, with a power of 80% and a confidence interval of 95%, a difference of 13.5% between the incidence of mutation of the GNA11 gene in patients with melanoma and healthy controls. (13.5% vs 0%). Overall, at least 51 patients with uveal melanoma and 51 controls will be recruited, for a total of at least 102 subjects.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| patients with uveal melanoma 51 patients with a diagnosed with uveal melanoma; of both sexes, aging more than 18 years. The exclusion criteria are: a) subjects with autoimmune diseases, tumors, diseases kidney, atherosclerosis; b) subjects undergoing anti-inflammatory therapies. |
Genetic: blood sample examination
droplet digital PCR in blood sample for research of mutations of GNA11 and GNAQ genes and the following microRNAs: miR - 506-514 cluster, hsamiR - 592 and hsa - miR - 199a - 5p.
|
| healthy controls 51 age sex matched controls, patients with diagnosed with cataracts; of both sexes, aging more than 18 years. The exclusion criteria are: a) subjects with autoimmune diseases, tumors, kidney diseases, atherosclerosis; b) subjects undergoing anti-inflammatory therapies. |
Genetic: blood sample examination
droplet digital PCR in blood sample for research of mutations of GNA11 and GNAQ genes and the following microRNAs: miR - 506-514 cluster, hsamiR - 592 and hsa - miR - 199a - 5p.
|
Outcome Measures
Primary Outcome Measures
- circulating GNA11 mutation detection through digital droplet PCR [at the diagnosis of uveal melanoma (first visit), through study completion, in an average of 1 year]
the incidence of GNA11 mutations in uveal melanoma patients and in controls
Secondary Outcome Measures
- micro RNA levels in serum [at the diagnosis of uveal melanoma (first visit), through study completion, in an average of 1 year]
the expression levels of circulating miRNAs (miR - 506-514 cluster, hsamiR - 592 and hsa - miR - 199a - 5p) in uveal melanoma patients and in controls
Eligibility Criteria
Criteria
Inclusion Criteria:
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subjects diagnosed with uveal melanoma
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both sexes
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age ≥ 18 years
Exclusion Criteria:
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- autoimmune diseases
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- tumors
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- kidney diseases
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- atherosclerosis
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- subjects undergoing anti-inflammatory therapies.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Eye Clinic, Azienda Policlinico San Marco | Catania | Italy | 95123 | |
| 2 | Eye Clinic University of Turin | Turin | Italy | ||
| 3 | Department of General and Pediatric Ophthalmology, Medical University of Lublin | Lublin | Poland |
Sponsors and Collaborators
- University of Catania
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- Diener-West M, Reynolds SM, Agugliaro DJ, Caldwell R, Cumming K, Earle JD, Hawkins BS, Hayman JA, Jaiyesimi I, Jampol LM, Kirkwood JM, Koh WJ, Robertson DM, Shaw JM, Straatsma BR, Thoma J; Collaborative Ocular Melanoma Study Group. Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26. Arch Ophthalmol. 2005 Dec;123(12):1639-43.
- Falzone L, Romano GL, Salemi R, Bucolo C, Tomasello B, Lupo G, Anfuso CD, Spandidos DA, Libra M, Candido S. Prognostic significance of deregulated microRNAs in uveal melanomas. Mol Med Rep. 2019 Apr;19(4):2599-2610. doi: 10.3892/mmr.2019.9949. Epub 2019 Feb 11.
- Krantz BA, Dave N, Komatsubara KM, Marr BP, Carvajal RD. Uveal melanoma: epidemiology, etiology, and treatment of primary disease. Clin Ophthalmol. 2017 Jan 31;11:279-289. doi: 10.2147/OPTH.S89591. eCollection 2017. Review.
- Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T, Obenauf AC, Wackernagel W, Green G, Bouvier N, Sozen MM, Baimukanova G, Roy R, Heguy A, Dolgalev I, Khanin R, Busam K, Speicher MR, O'Brien J, Bastian BC. Mutations in GNA11 in uveal melanoma. N Engl J Med. 2010 Dec 2;363(23):2191-9. doi: 10.1056/NEJMoa1000584. Epub 2010 Nov 17.
- 71/2020/PO