Understanding the Transition from Normal Melanocytes to Nevus to Melanoma

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.

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.

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