NRAS mutations in primary and metastatic melanomas of Japanese patients

Hisashi Uhara1, Atsuko Ashida, Hiroshi Koga

  • 1Department of Dermatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.

Abstract

Insights

NRAS mutations are less common in Japanese melanoma patients compared to Caucasians. Genotyping both primary and metastatic melanoma lesions is crucial for identifying patients eligible for targeted therapies.

Area of Science:

  • Oncology
  • Genetics
  • Dermatology

Background:

  • The MAPK signaling pathway is a target for melanoma treatment, particularly MEK inhibitors for NRAS-mutated melanoma.
  • Identifying gene mutations is key for molecular-targeted therapies.
  • Current genetic mutation data predominantly comes from Caucasian populations, with limited data on Asian populations.

Purpose of the Study:

  • To investigate the prevalence of NRAS mutations in primary and metastatic melanoma lesions among Japanese patients.

Main Methods:

  • Collected clinical melanoma specimens from 127 Japanese patients.
  • Analyzed primary, metastatic, and paired primary/metastatic lesions.
  • Assessed NRAS mutations in exons 1 and 2 using polymerase chain reaction and Sanger sequencing.

Main Results:

  • The overall incidence of NRAS mutations was 7.1%, with NRAS (Q61) being the most common alteration (77.8%).
  • NRAS mutations were most frequent in acral melanomas (9.3%) and melanomas without chronic sun damage (7.0%).
  • Mutations were more prevalent on extremities, and one case showed differing NRAS sequences between primary and metastatic lesions.

Conclusions:

  • NRAS mutation frequency is lower in the Asian population compared to Caucasian patients.
  • Melanoma exhibits heterogeneity, necessitating genotyping of both primary and metastatic sites.
  • Genotyping aids in identifying suitable candidates for molecular-targeted melanoma therapies.

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