Identification of New Candidate Genes for Hereditary Predisposition to Uveal Melanoma

NCT06550674 | Recruiting

• 1 other identifier: 2024-A00030-47
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Uveal Melanoma

Keywords

uveal melanoma; hereditary predisposition; candidate genes identification

Outcome Measures

Primary Outcomes (1)

• 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

  At baseline

Secondary Outcomes (1)

• 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

Study Arms (1)

constitutional genetic analysis

EXPERIMENTAL

Constitutional genetic exome analysis will be performed on the blood sample. If necessary, an analysis on a second independent sample (jugal smear) will be carried out if a probably pathogenic or pathogenic variant in a hereditary cancer predisposition gene is identified.

Genetic: Constitutional exome analysis

Interventions

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.

constitutional genetic analysis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Jean Perrin: lead
• Association Nationale des Patients atteints de cancers de l'oeil (A.N.P.A.C.O.): collaborator

Study Sites (1)

Centre Jean PERRIN

Clermont-Ferrand, Puy-de-Dôme, 63011, France

RECRUITING

Related Publications (1)

• Godiveau M, Ginzac A, Bidet Y, Ponelle-Chachuat F, Privat M, Durando X, Cavaille M, Lepage M. Identification of new candidate genes for the hereditary predisposition to uveal melanoma: IGCMU trial. Front Oncol. 2025 Jan 24;15:1538924. doi: 10.3389/fonc.2025.1538924. eCollection 2025.

  PMID: 39926282 DERIVED

MeSH Terms

Conditions

Uveal Melanoma

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Study Officials

• Mathis LEPAGE, Dr

  Centre Jean Perrin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Angeline GINZAC COUVÉ

CONTACT

0473278005; angeline.ginzac@clermont.unicancer.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 5, 2024
• First Posted: August 13, 2024
• Study Start: October 29, 2024
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)