Identification of New Candidate Genes for Hereditary Predisposition to Uveal Melanoma

ConditionUveal Melanoma

Trial statusRecruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age18+

SponsorCentre Jean Perrin

About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

Constitutional exome analysis
Genetic
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.

Treatment groups

50 Participants

are divided into 1 treatment group

Group A: constitutional genetic analysisExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

Identify new candidate genes for hereditary cancer predisposition in patients with uveal melanoma by constitutional exome analysis

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

Time frame

At baseline

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.

Number of patients with a mutation on BRCA1, BRCA2, CHEK2, PALB2, POT1, MSH6 or MLH1

Time frame

At baseline

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Centre Jean Perrin

Lead sponsor

Association Nationale des Patients atteints de cancers de l'oeil (A.N.P.A.C.O.)

Collaborator

Source ClinicalTrials.gov

Apply now