title: BRAF V600 mutations and pathological features in Japanese melanoma patients.
abstract: Ultraviolet radiation is a risk factor for BRAF V600 mutations frequently found in melanomas that cause constitutive BRAF activation. Primary sites of melanoma and the frequency of BRAF mutations might differ between races. Melanoma is rare in Japan (1500-2000 cases/year compared with 132 000/year worldwide) and the frequency and distribution of BRAF V600 mutations are unknown. We aimed to investigate the frequency of BRAF V600 mutations in a cohort of Japanese patients with melanoma and determine the relationship between mutations and clinical/pathologic features. DNA was extracted from 80 formalin-fixed, paraffin-embedded tumours from individuals diagnosed with melanoma. BRAF V600 mutations were detected using the Cobas 4800 System with z480 Analyzer and Cobas 4800 BRAF V600 Mutation Test reagents. BRAF V600 mutations were detected in 41.8% of tested tumours, with an invalid rate of 1.3%. The mutation rate was more than 60% in patients aged less than 60 years and more than 36% in patients with stage III/IV disease. No sex difference in the mutation rate was observed. BRAF V600 mutations were detected in 18.8% of acral lentiginous melanomas (ALMs), 64.7% of superficial spreading melanomas, 50.0% of lentigo maligna melanomas and 20.0% of nodular melanomas. Although the mutation rate was low in ALMs, 36.4% were mutation positive at stage III/IV compared with 9.5% at stage I/II. This study confirmed associations among BRAF V600 mutations, pathological features and subtypes of melanoma. BRAF V600 mutations were more frequent in late-stage ALMs than in early-stage ALMs. Superficial spreading melanomas had similar mutation rates at all stages. These insights suggest improved treatment predictions for stage III/IV melanoma patients.
authors: Departments of aDermatologic Oncology bPathology and Clinical Laboratories, National Cancer Center Hospital cRoche Diagnostics K.K. dChugai Pharmaceutical Co. Ltd, Tokyo, Japan.
authors: Naoya
authors: N
authors: Yamazaki
authors: Ryota
authors: R
authors: Tanaka
authors: Arata
authors: A
authors: Tsutsumida
authors: Kenjiro
authors: K
authors: Namikawa
authors: Hironobu
authors: H
authors: Eguchi
authors: Wataru
authors: W
authors: Omata
authors: Kohei
authors: K
authors: Oashi
authors: Toru
authors: T
authors: Ogawa
authors: Amiko
authors: A
authors: Hayashi
authors: Noriyuki
authors: N
authors: Nakamura
authors: Koji
authors: K
authors: Tsuta
mesh_terms: D000368:Aged; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage; D007564:Japan; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation; D009362:Neoplasm Metastasis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012307:Risk Factors; D012878:Skin Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D013449:Sulfonamides / Q000008:administration & dosage; D014466:Ultraviolet Rays; D000077484:Vemurafenib
chemical_list: D007211:Indoles; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf