The Role of Genetic Mutations and of Circulating mRNAs in Uveal Melanoma

Study Overview
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Brief Summary
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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: to identify the circulating somatic mutations associated with uveal melanoma; to identify the de-regulated miRNAs associated with uveal melanoma; to evaluate the diagnostic and prognostic role of the identified genetic and epigenetic markers; to identify possible therapeutic targets.

Detailed Description
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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.

Official Title
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The Role of Genetic Mutations and of Circulating mRNAs in Uveal Melanoma

Conditions
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Uveal Melanoma

Intervention / Treatment
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* Genetic: blood sample examination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: subjects diagnosed with uveal melanoma both sexes age ≥ 18 years Exclusion Criteria: a) autoimmune diseases b) tumors c) kidney diseases d) atherosclerosis e) subjects undergoing anti-inflammatory therapies.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| patients with uveal melanoma<br>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<br>* 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.<br>|
| healthy controls<br>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<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| circulating GNA11 mutation detection through digital droplet PCR | the incidence of GNA11 mutations in uveal melanoma patients and in controls | at the diagnosis of uveal melanoma (first visit), through study completion, in an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| micro RNA levels in serum | the expression levels of circulating miRNAs (miR - 506-514 cluster, hsamiR - 592 and hsa - miR - 199a - 5p) in uveal melanoma patients and in controls | at the diagnosis of uveal melanoma (first visit), through study completion, in an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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uveal melanoma, GNA11 mutation, GNAQ mutation, micro RNA