Uhara Hisashi, Ashida Atsuko, Koga Hiroshi, Ogawa Eisaku, Uchiyama Aya, Uchiyama Ryuhei, Hayashi Koichi, Kiniwa Yukiko, Okuyama Ryuhei
Department of Dermatology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan.
Int J Clin Oncol. 2014;19(3):544-8. doi: 10.1007/s10147-013-0573-2. Epub 2013 Jun 6.
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.
The aim of the present study was to examine NRAS mutations in primary and metastatic lesions of Japanese melanoma patients.
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.
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.
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.
黑色素瘤中丝裂原活化蛋白激酶（MAPK）信号通路的特征研究促使了用于治疗NRAS 突变型黑色素瘤的 MEK 抑制剂的开发。分子靶向治疗的成功凸显了识别靶基因突变的必要性。目前大多数关于基因突变的数据来自白种人黑色素瘤患者，对亚洲人群的筛查有限。
本研究旨在检测日本黑色素瘤患者原发性和转移性病灶中的NRAS 突变。
收集了 127 例日本患者的临床黑色素瘤标本，包括原发性（n = 67）、转移性（n = 25）以及配对的原发性和转移性病灶（n = 35）。通过聚合酶链反应和桑格测序评估外显子 1 和 2 中的NRAS 突变。
NRAS 突变发生率为 7.1%。NRAS（Q61）是主要的基因改变（77.8%）。NRAS 突变最常见于肢端黑色素瘤（9.3%），其次是无慢性日光损伤的黑色素瘤（7.0%）和黏膜黑色素瘤（4.8%），而在有慢性日光损伤的黑色素瘤中未检测到。此外，NRAS 突变在四肢比在其他部位更普遍。1 例患者转移病灶中的NRAS 序列与原发肿瘤不匹配。
亚洲人群中NRAS 突变频率低于白种人患者。观察到的黑色素瘤异质性表明，对原发性和转移性病灶进行基因分型对于识别分子靶向治疗的候选患者很重要。
