Identification of New Candidate Genes for Hereditary Predisposition to Uveal Melanoma

Not Applicable

Recruiting

• Conditions: Uveal Melanoma

• Registration Number: NCT06550674
• Lead Sponsor: Centre Jean Perrin

Brief Summary

Only 20% of familial uveal melanomas are explained by a hereditary predisposition, implying the presence of as yet unknown hereditary predispositions. This hypothesis is reinforced by epidemiological studies revealing an excess risk of prostate cancer, thyroid cancer and leukemia in patients who have developed uveal melanoma, even though these cancers are not part of the tumor spectrum of known hereditary predispositions to uveal melanoma (BAP1, MBD4). The identification of new candidate genes, once validated, would enable us to offer these families appropriate surveillance.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-08-05
• Study First Submitted QC: 2024-08-08
• Study First Posted: 2024-08-13
• Study Start: 2024-10-29
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-04
• Last Update Posted: 2025-06-06
• Primary Completion: 2025-10
• Study Completion: 2026-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Patient with a personal history of uveal melanoma (newly diagnosed, under treatment or in follow-up)
• Enrolled in or benefiting from a social security scheme

Exclusion Criteria

• Causal pathogenic variation identified in BAP1 or MBD4
• Patient does not consent to constitutional genetic analysis for diagnostic purposes
• Patient not consenting to a constitutional genetic analysis for research purposes
• Pregnant and breast-feeding women
• Patients under guardianship or trusteeship

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Identify new candidate genes for hereditary cancer predisposition in patients with uveal melanoma by constitutional exome analysis	At baseline	Variants of interest are selected from the data using the following filter: * Variant with frequency \< 1% (GnomAD); * Shared by at least 2 sufferers in the cohort; * Truncating (nonsense, with frame shift, on a canonical splice site -2, -1 and +1 +2); * Missense from a list of "cancer" genes and Combined Annotation Dependent Depletion (CADD) score \> 20 (COSMIC Tier1 and Tier2); Variants will be interpreted using various databases and prediction tools: * Functions: genecards, pubmed, uniprot; * Expression profiles: cbioportal, GEPIA; * For splice variants: CADD, Splice AI; * For exonic variants: CADD, SIFT, Polyphene

Secondary Outcome Measures

Name	Time	Method
Explore genes known to be involved in other cancer predisposition already described in the occurrence of uveal melanoma, but whose association has not yet been established with certainty.	At baseline	Number of patients with a mutation on BRCA1, BRCA2, CHEK2, PALB2, POT1, MSH6 or MLH1

Trial Locations

Locations (1)

Centre Jean PERRIN; 🇫🇷 Clermont-Ferrand, Puy-de-Dôme, France