Genetic Analysis of Melanoma Types Using Japanese Genomic Database

Area of Science:

• Oncology
• Genetics
• Immunotherapy

Background:

• Head and neck mucosal melanoma (HNMUM) is a rare subtype with distinct characteristics.
• Understanding its genetic landscape and response to therapy is crucial for improving patient outcomes.
• Comparison with more common melanoma types, skin melanoma (SKM) and ocular melanoma (OM), provides valuable insights.

Purpose of the Study:

• To compare genetic mutations, tumor mutation burden (TMB), and the efficacy of molecular targeted drugs and immune checkpoint inhibitors (ICIs) in HNMUM versus SKM and OM.
• To identify specific genetic alterations prevalent in HNMUM.
• To evaluate the therapeutic potential of ICIs in HNMUM.

Main Methods:

• Analysis of genetic alterations and TMB in 72 HNMUM, 366 SKM, and 31 OM patients using FoundationOne CDx next-generation sequencing.
• Comparison of mutation profiles, TMB values, and survival data across the three melanoma subtypes.
• Assessment of treatment responses to molecular targeted drugs and ICIs.

Main Results:

• Top mutations in HNMUM include RAD21, NBN, and MYC; mutation profiles are more similar to OM than SKM.
• TMB values did not significantly differ across HNMUM, SKM, and OM (5.7±2.1, 4.1±0.2, and 3.4±0.9, respectively).
• Median survival times for distant metastases varied: HNMUM (803 days), SKM (1413 days), and OM (1138 days).

Conclusions:

• HNMUM exhibits a genetic profile more aligned with OM than SKM.
• No significant differences in TMB or survival rates were observed concerning ICI efficacy among the three melanoma types.
• Current treatment strategies utilizing ICIs appear appropriate for HNMUM.