Targeted next generation sequencing (NGS) to classify melanocytic neoplasms

Area of Science:

• Oncology
• Genetics
• Dermatopathology

Background:

• Melanocytic tumors require accurate diagnosis for appropriate treatment.
• Next-generation sequencing (NGS) offers a comprehensive approach to genetic profiling.
• Distinguishing benign from malignant melanocytic lesions can be challenging.

Purpose of the Study:

• To pilot a laboratory-developed, pan-solid-tumor NGS test as a diagnostic aid for melanocytic tumors.
• To evaluate the utility of NGS in differentiating benign and malignant melanocytic lesions.
• To compare NGS performance with existing diagnostic methods like FISH.

Main Methods:

• A cohort of 31 melanocytic tumors (nevi, Spitz tumors, melanomas) was analyzed using a custom NGS panel.
• Genetic alterations including small nucleotide variants, fusions, and amplifications were quantified.
• NGS results were compared with histopathological diagnoses and Fluorescence In Situ Hybridization (FISH) findings.

Main Results:

• NGS successfully analyzed all tumor samples, yielding satisfactory results.
• Significant differences in small nucleotide variant counts were observed between melanoma and benign lesions.
• Specific genetic alterations (e.g., BRAF, NRAS, NF1 mutations, amplifications) were associated with melanoma and malignant Spitz tumors.
• NGS criteria correctly classified all malignant lesions in the study.
• Concordance with FISH was observed in 10 out of 12 cases.

Conclusions:

• NGS is a promising diagnostic adjunct for melanocytic tumors, comparable to FISH.
• The developed NGS-based criteria demonstrated high accuracy in classifying malignant lesions.
• Further validation with larger patient cohorts is warranted to establish NGS as a standard diagnostic tool.