Understanding the Transition from Normal Melanocytes to Nevus to Melanoma

Recruiting

• Conditions: Congenital Melanocytic Nevi; Melanoma, Skin; Nevi and Melanomas
• Interventions: Genetic: Methylomics; Genetic: RNA sequencing; Genetic: Spatial transcriptomics; Genetic: Liquid biopsy

• Registration Number: NCT06605417
• Lead Sponsor: Fundacion Clinic per a la Recerca Biomédica

Brief Summary

The primary objective of this study is to identify the molecular identity profiles of all cellular states that characterize the progression from benign nevi to malignant melanoma in CAYA patients with L/GCMN. The secondary objectives are:

* To longitudinally characterize the cell-free DNA (cfDNA) from CAYA patients.

* To improve the early diagnosis and treatments for intermediate conditions such as L/GCMN through evidence-based interpretation of personal risk from endogenous or exogenous sources.

* To test pre-clinical strategies to best model and improve patient response.

Detailed Description

NevustoMel is an international multicentric retrospective cohort study with molecular and experimental design. It will involve the genomic characterization of cell-free DNA and affected tissues from patients. Methylomics and single-cell multi-omics will be used to identify co-existing molecular (transcriptional and epigenomic) states at single-cell level and will be generated from affected tissues. These results will be exploited using machine learning-assisted integration of multi-modal transcriptomics, epigenomics and spatial information. Integrated analyses of single-nucleus RNA sequencing from a selection of frozen tissues and spatial transcriptomics on formalin-fixed paraffin-embedded samples will allow the comparison of the findings to ground-state Human Developmental Cell Atlas data. Distinctions will be validated either with in situ hybridization (such as RNA sequencing) or immunostaining on test cohort tissues. These results will be complemented with in vitro functional analyses, high throughput sequencing and bioinformatic analyses.

Study Timeline

• Study Start: 2024-01-01
• Status Verified: 2024-09
• Study First Submitted: 2024-09-18
• Study First Submitted QC: 2024-09-18
• Study First Posted: 2024-09-20
• Last Update Submitted: 2025-02-25
• Last Update Posted: 2025-02-27
• Primary Completion: 2026-03-31
• Study Completion: 2026-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
L/GCMN	Methylomics	Patients with congenital nevus with estimated size of 20 cm or more in adulthood (\> 18 years old)
L/GCMN	RNA sequencing	Patients with congenital nevus with estimated size of 20 cm or more in adulthood (\> 18 years old)
L/GCMN	Spatial transcriptomics	Patients with congenital nevus with estimated size of 20 cm or more in adulthood (\> 18 years old)
L/GCMN	Liquid biopsy	Patients with congenital nevus with estimated size of 20 cm or more in adulthood (\> 18 years old)
Melanoma	Methylomics	Patients affected with Spitz-type or conventional melanomas in patients under 30 years of age
Melanoma	RNA sequencing	Patients affected with Spitz-type or conventional melanomas in patients under 30 years of age
Melanoma	Spatial transcriptomics	Patients affected with Spitz-type or conventional melanomas in patients under 30 years of age
Melanoma	Liquid biopsy	Patients affected with Spitz-type or conventional melanomas in patients under 30 years of age

Primary Outcome Measures

Name	Time	Method
Molecular identity profiles	26 months	Molecular identity profiles of all cellular states that characterize the progression from benign nevi to malignant melanoma in children, adolescents and young adults (CAYA) patients with large/giant congenital melanocytic nevi (L/GCMN)

Secondary Outcome Measures

Name	Time	Method
cfDNA profiles	26 months	Longitudinal characterization of the cell-free DNA (cfDNA) of CAYA patients
Improve the early diagnosis and treatment of L/GCMN	26 months	Improve the early diagnosis and treatments for intermediate conditions such as L/GCMN through evidence-based interpretation of personal risk from endogenous or exogenous sources.
Test pre-clinical strategies for L/GCMN	26 months	Test pre-clinical strategies to best model and improve patient response with intermediate lesions such as L/GCMN

Trial Locations

Locations (2)

French National Institute of Health and Medical Research; 🇫🇷 Marseille, France

Hospital Clínic de Barcelona (Dermatology service); 🇪🇸 Barcelona, Spain