TY - JOUR
T1 - BRAF point mutations in primary melanoma show different prevalence by subtype
AU - Sasaki, Yoshinori
AU - Niu, Chunbo
AU - Makino, Rui
AU - Kudo, Chieko
AU - Sun, Chunlan
AU - Watanabe, Hiroshi
AU - Matsunaga, Jun
AU - Takahashi, Kazuhiro
AU - Tagami, Hachiro
AU - Aiba, Setsuya
AU - Horii, Akira
N1 - Funding Information:
We are grateful to Dr Takashi Yamada at the Department of Pathology, Osaka Medical College (Takatsuki, Japan), for providing a melanoma cell line DEOC-1. We are also grateful to Machiko Obata and Yumiko Yoshino at Department of Dermatology, Tohoku University School of Medicine (Sendai, Japan) for their technical assistance, and to Dr Barbara Lee Smith Pierce at the University of Maryland University College for editorial work in the preparation of this manuscript. This work was supported by Japanese Ministry of Education, Culture, Sports, Science, and Technology.
PY - 2004/7
Y1 - 2004/7
N2 - To elucidate the biological significance of activating mutations of BRAF in human malignant tumors, we performed a mutation analysis using 43 cell lines established from tumors that had developed in several kinds of human organs. Because the same V599E point mutation was observed in three of six melanoma cell lines and no such mutations were observed in other types of cancers, we focused further on melanoma, performed mutation analyses of NRAS, KRAS, CTNNB1, and p16/p14ARF in these cell lines, and found one NRAS mutation and three p16/p14ARF mutations. We further searched for mutations of BRAF and NRAS in 35 primary sporadic melanomas from 35 Japanese patients and detected the V599E BRAF point mutation in only nine (26%) of them. Significant differences in mutation frequency were observed among four histological subtypes; four (50%) of eight superficially spreading melanoma and five (33%) of 15 acral lentiginous melanoma had the mutation, whereas none of 12 other types (six nodular melanoma, five lentigo melanoma, and one mucosal melanoma) had it. The BRAF mutation was observed frequently even in small lesions, indicating that activation of this gene may be one of the early events in the pathogenesis of some melanomas.
AB - To elucidate the biological significance of activating mutations of BRAF in human malignant tumors, we performed a mutation analysis using 43 cell lines established from tumors that had developed in several kinds of human organs. Because the same V599E point mutation was observed in three of six melanoma cell lines and no such mutations were observed in other types of cancers, we focused further on melanoma, performed mutation analyses of NRAS, KRAS, CTNNB1, and p16/p14ARF in these cell lines, and found one NRAS mutation and three p16/p14ARF mutations. We further searched for mutations of BRAF and NRAS in 35 primary sporadic melanomas from 35 Japanese patients and detected the V599E BRAF point mutation in only nine (26%) of them. Significant differences in mutation frequency were observed among four histological subtypes; four (50%) of eight superficially spreading melanoma and five (33%) of 15 acral lentiginous melanoma had the mutation, whereas none of 12 other types (six nodular melanoma, five lentigo melanoma, and one mucosal melanoma) had it. The BRAF mutation was observed frequently even in small lesions, indicating that activation of this gene may be one of the early events in the pathogenesis of some melanomas.
KW - BRAF
KW - CTNNB1
KW - Melanoma
KW - NRAS
KW - p14
KW - p16
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UR - http://www.scopus.com/inward/citedby.url?scp=3042600380&partnerID=8YFLogxK
U2 - 10.1111/j.0022-202X.2004.22722.x
DO - 10.1111/j.0022-202X.2004.22722.x
M3 - Article
C2 - 15191558
AN - SCOPUS:3042600380
VL - 123
SP - 177
EP - 183
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 1
ER -