Congenital Melanocytic Nevi, Melanoma, Skin, Nevi and Melanomas
Conditions
Keywords
Congenital melanocytic nevi, Melanoma, Liquid biopsy, cfDNA, Methylomics, L/GCMN, RNAseq, Molecular profiles
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.
Interventions
GENETICMethylomics
Methylomics analysis of FFPE blocks and frozen tissues
GENETICRNA sequencing
RNA sequencing of FFPE blocks and frozen tissues
GENETICSpatial transcriptomics
Spatial transcriptomics of FFPE blocks and frozen tissues
GENETICLiquid biopsy
cfDNA characterization extracted from blood/saliva
Sponsors
Institut National de la Santé Et de la Recherche Médicale, France
University Hospital Tuebingen
University of Florence
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
University Of Perugia
German Cancer Research Center
Karolinska Institutet
Maria Sklodowska-Curie National Research Institute of Oncology
Institut Curie
Medical University of Gdansk
Princess Maxima Center for Pediatric Oncology
Institut Català d'Oncologia
Fundacion Clinic per a la Recerca Biomédica
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
France, Spain
Contacts
Primary ContactSusana Puig Sardà, MD, PhD
Backup ContactAdrián López Canosa, PhD
Outcome results
None listed