Constitutional exome analysis: For each patient included:
* A family tree is drawn up, reporting personal and family histories of cancer. The patient's anatomopathological reports, related to his or her tumor lesions, are retrieved, in order to confirm/clarify individual or family diagnoses.
* A blood sample and a jugal smear are taken to enable constitutional genetic exome analysis for research purposes.
Study 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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
Primary outcome measure(s)
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
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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