Clinical characteristics associated with BRAF, NRAS and KIT mutations in Japanese melanoma patients.
BACKGROUND
The importance of the genetic background of melanoma cells to the individual susceptibility to treatment has become apparent. In Caucasians, BRAF mutations are frequently detected in lesions on the skin of younger patients compared to NRAS and KIT mutations. However, clinical and pathological characteristics associated with BRAF, NRAS and KIT mutations have not been fully evaluated in East Asians.


OBJECTIVE
To clarify clinical and pathological characteristics associated with BRAF, NRAS and KIT mutations in Japanese melanoma patients.


METHODS
Clinical data were retrospectively collected from 11 hospitals in Japan. BRAF, NRAS and KIT mutations were evaluated with polymerase chain reaction and Sanger sequencing. The relationships between these gene mutations and pathological and clinical findings were analyzed.


RESULTS
The number of cases examined was 171 (primary: 135, metastases: 11, paired: 25), and all were Japanese patients. The detection rates of BRAF, NRAS and KIT mutations were 30.4%, 12.3% and 12.9%, respectively. Compared with the wild type, the presence of BRAF mutations was significantly associated with younger age (median, 50.0 years vs. 70.0 years, p<0.001). BRAF mutation was frequently detected in the lesions of the scalp (80%; 4/5), trunk (72.0%; 18/25), extremities (56.7%; 17/30) and neck (44.4%; 4/9), and the least prevalent were the face (22.2%; 2/9), nail (12.5%; 3/24), palm or sole (8.9%; 4/45) and mucosa (0%). NRAS mutations were prevalent in the face (33.3%) and palm or sole (20.0%), and the median age of these patients was 70.5 years. A KIT mutation was observed in the nail apparatus (25%), palm or sole (15.6%) and mucosa (18.2%). The median age of the patients with a KIT mutation was 63.0 years. Heterogeneity of mutations between primary and metastatic lesions was detected in six of 25 cases (24%). Solar elastosis was identified in 12 of 71 cases (15.3%), among which four cases harbored BRAF(V600E) (2 cases), BRAF(V600K), NRAS(Q61K) or NRAS(Q61L), respectively.


CONCLUSIONS
Some clinical characteristics associated with BRAF, NRAS and KIT mutations were observed in Japanese patients, and we observed both similarities to and differences from those of Caucasians. Our findings could provide useful information in efforts to clarify the tumor genesis of malignant melanomas.
Department of Dermatology, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano 390-8621, Japan.
Kaori
K
Sakaizawa
Department of Dermatology, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano 390-8621, Japan.
Atsuko
A
Ashida
Department of Dermatology, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano 390-8621, Japan.
Aya
A
Uchiyama
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Takamichi
T
Ito
Department of Dermatology, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
Yasuhiro
Y
Fujisawa
Department of Dermatology, Saitama Medical University, 38, Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan.
Dai
D
Ogata
Department of Dermato-Oncology/Dermatology, Kagoshima Medical Center, 8-1, Shiroyama-cho, Kagoshima 892-0853, Japan.
Shigeto
S
Matsushita
Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima 890-8520, Japan.
Kazuyasu
K
Fujii
Department of Dermatology and Plastic Surgery, Faculty of Life Sciences, Kumamoto University, 1-1-1, Honjo, Kumamoto 860-0811, Japan.
Satoshi
S
Fukushima
Department of Dermatology, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Yoshitsugu
Y
Shibayama
Department of Dermatology, Toyama Prefectural Central Hospital, 2-2-78, Nishinagae, Toyama 930-8550, Japan.
Naohito
N
Hatta
Department of Dermatology, Niigata Cancer Center Hospital, 2-15-3, Kawagishi-cho, Chuo-ku, Niigata 951-8566, Japan.
Tatsuya
T
Takenouchi
Department of Dermatology, Asahikawa Medical University, 1-1-1, Higashinijo, Midorigaoka, Asahikawa 078-8510, Japan.
Jiro
J
Uehara
Department of Dermatology, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano 390-8621, Japan.
Ryuhei
R
Okuyama
Department of Dermatologic Oncology, National Cancer Center Hospital, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
Naoya
N
Yamazaki
Department of Dermatology, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano 390-8621, Japan. Electronic address: uhara@shinshu-u.ac.jp.
Hisashi
H
Uhara
D000368:Aged; D044466:Asian People / Q000235:genetics; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology
D008565:Membrane Proteins; D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
BRAF; Japanese; KIT; Melanoma; Mitogen-activated protein kinase (MAPK); NRAS