Understanding the Transition from Normal Melanocytes to Nevus to Melanoma (NevustoMel)

Understanding the Transition from Normal Melanocytes to Nevus to Melanoma (NevustoMel)

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.

Study Overview

• Status: Recruiting
• Conditions: Nevi and Melanomas; Melanoma, Skin; Congenital Melanocytic Nevi
• Intervention / Treatment: Genetic: Methylomics; Genetic: RNA sequencing; Genetic: Spatial transcriptomics; Genetic: Liquid biopsy

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 Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Adrián López Canosa, PhD; Email: lopez64@recerca.clinic.cat
• Study Contact Backup: Name: Susana Puig Sardà, MD, PhD; Phone Number: +34932275400; Email: spuig@clinic.cat

Study Locations

• France
  • Marseille, France
    • Recruiting
    • French National Institute of Health and Medical Research
    • Contact: Heather Etchevers, PhD; Phone Number: +33491324937; Email: heather.etchevers@inserm.fr
• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital Clínic de Barcelona (Dermatology service)
    • Contact: Susana Puig Sardà, PhD, MD; Phone Number: +34932275400; Email: spuig@clinic.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Review and/or analysis of pre-existing medical records, biological samples and data collected from patients that have been visited at the different participating hospitals.

Description

Inclusion criteria:

• Congenital nevus with estimated size of 20 cm
• Be over 18 years of age

Exclusion criteria:

• No available biological material
• Not having signed the informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
L/GCMN; Patients with congenital nevus with estimated size of 20 cm or more in adulthood (> 18 years old)	Genetic: Methylomics; Methylomics analysis of FFPE blocks and frozen tissues; Genetic: RNA sequencing; RNA sequencing of FFPE blocks and frozen tissues; Genetic: Spatial transcriptomics; Spatial transcriptomics of FFPE blocks and frozen tissues; Genetic: Liquid biopsy; cfDNA characterization extracted from blood/saliva
Melanoma; Patients affected with Spitz-type or conventional melanomas in patients under 30 years of age	Genetic: Methylomics; Methylomics analysis of FFPE blocks and frozen tissues; Genetic: RNA sequencing; RNA sequencing of FFPE blocks and frozen tissues; Genetic: Spatial transcriptomics; Spatial transcriptomics of FFPE blocks and frozen tissues; Genetic: Liquid biopsy; cfDNA characterization extracted from blood/saliva

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular identity profiles	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)	26 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cfDNA profiles	Longitudinal characterization of the cell-free DNA (cfDNA) of CAYA patients	26 months
Improve the early diagnosis and treatment of L/GCMN	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.	26 months
Test pre-clinical strategies for L/GCMN	Test pre-clinical strategies to best model and improve patient response with intermediate lesions such as L/GCMN	26 months

Collaborators and Investigators

• Sponsor: Fundacion Clinic per a la Recerca Biomédica
• Collaborators: Karolinska Institutet; Fondazione IRCCS Istituto Nazionale dei Tumori, Milano; Institut Català d'Oncologia; German Cancer Research Center; University Of Perugia; University Hospital Tuebingen; University of Florence; Princess Maxima Center for Pediatric Oncology; Medical University of Gdansk; Institut Curie; Maria Sklodowska-Curie National Research Institute of Oncology; Institut National de la Santé Et de la Recherche Médicale, France

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: September 18, 2024
• First Submitted That Met QC Criteria: September 18, 2024
• First Posted (Actual): September 20, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 25, 2025
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Melanoma; Liquid biopsy; RNAseq; cfDNA; Molecular profiles; L/GCMN; Congenital melanocytic nevi; Methylomics
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Skin Neoplasms; Melanoma; Nevus; Nevus, Pigmented; Nevi and Melanomas
• Other Study ID Numbers: HCB/2023/0843; HORIZON-MISS-2021-CANCER-02-03 (Other Grant/Funding Number: European Comission)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No