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Updated: May 10, 2026

Spatial and Temporal Control of Murine Melanoma Initiation from Mutant Melanocyte Stem Cells
Published on: June 7, 2019
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.
Background:
Characterization of the MAPK signaling pathway in melanoma has led to the development of MEK inhibitors for the treatment of NRAS-mutated melanoma. The success of molecular-targeted therapies underscores the need to identify mutations in target genes. Most of the current data on genetic mutations have been obtained from Caucasian melanoma patients, and screenings of Asian populations are limited.
Objective:
The aim of the present study was to examine NRAS mutations in primary and metastatic lesions of Japanese melanoma patients.
Methods:
Clinical melanoma specimens were collected from 127 Japanese patients, including primary (n = 67), metastatic (n = 25) and paired primary and metastatic lesions (n = 35). NRAS mutations in exons 1 and 2 were assessed by polymerase chain reaction and Sanger sequencing.
Results:
The incidence of NRAS mutations was 7.1 %. NRAS (Q61) was the predominant genetic alteration (77.8 %). NRAS mutations were most frequently detected in acral melanomas (9.3 %), followed by melanomas without chronic sun-induced damage (7.0 %) and mucosal melanomas (4.8 %), and were not detected in melanomas with chronic sun-induced damage. In addition, NRAS mutations were more prevalent in the extremities than in other sites. The NRAS sequence in metastatic lesions did not match that of the primary tumor in one case.
Conclusion:
The frequency of NRAS mutations is lower in the Asian population than in Caucasian patients. The observed heterogeneity of melanoma suggests that genotyping of both primary and metastatic lesions is important to identify candidate patients for molecular-targeted therapies.
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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