Identification of New Candidate Genes for Hereditary Predisposition to Uveal Melanoma
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Uveal Melanoma
- Sponsor
- Centre Jean Perrin
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Identify new candidate genes for hereditary cancer predisposition in patients with uveal melanoma by constitutional exome analysis
- Status
- Active, not recruiting
- Last Updated
- 5 months ago
Overview
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.
Investigators
Eligibility Criteria
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
Outcomes
Primary Outcomes
Identify new candidate genes for hereditary cancer predisposition in patients with uveal melanoma by constitutional exome analysis
Time Frame: 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 Outcomes
- 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)