NGS-Based Analysis of Atypical Deep Penetrating Nevi

Area of Science:

• Oncology
• Dermatopathology
• Genetics

Background:

• Deep penetrating nevi (DPNs) are rare melanocytic neoplasms with unique cyto-architectural features and WNT pathway activation.
• The genomic profile and metastatic potential of DPNs remain incompletely understood.

Purpose of the Study:

• To investigate the genomic profile of atypical DPNs.
• To explore potential associations between genetic mutations and histopathological features or metastatic potential.

Main Methods:

• Next-generation sequencing (NGS) using the Ion AmpliSeq™ Comprehensive Cancer Panel was performed on a cohort of 21 atypical DPNs.
• Analysis focused on mutations in key oncogenic pathways including WNT and MAP kinase.

Main Results:

• High frequencies of mutations were observed in β-catenin exon 3 (95%) and MAP kinase pathway genes (71%).
• Isocitrate dehydrogenases 1 (IDH1) mutations were found in 38% of cases, often co-existing with BRAF/HRAS mutations.
• The single case with progressive nodal disease harbored alterations in the β-catenin pathway, IDH1, and NRAS.

Conclusions:

• Atypical DPNs show low genetic heterogeneity with frequent mutations in the β-catenin and MAP kinase pathways.
• No significant associations were found between specific gene mutations and histopathological features.
• The role of NRAS or IDH1 mutations in DPN progression to melanoma warrants further investigation in larger cohorts.