title: Mutational profiling of acral melanomas in Korean populations.
abstract: The proportion of acral melanoma (AM) is much higher in Asian populations than in Caucasian populations. Although mutational profiles associated with AM have been discovered in Caucasian populations, knowledge of its genetic alterations in Asian populations is limited. To describe the molecular nature of AM in Korean patients, we performed mutational profiling of AM and matched normal tissues in patients. Fifty-one formalin-fixed paraffin-embedded AM samples and 32 matched pairs from patients' saliva DNA were analysed by next-generation sequencing. Only mutations confirmed via digital droplet PCR or in BRAF, KIT and NRAS, the most frequently altered cancer genes in cutaneous melanoma, were considered as positive. The relationship between mutational status and clinicopathological features were examined. Of the 47 AM patients screened, alteration of BRAF, NRAS and KIT genes was observed in 6.4%, 4.3% and 8.5%, respectively. We also tested matched normal tissues of patients to identify tumor-specific mutations. Examination of the mutational profile in a cohort of 28 primary melanomas and matched normal controls found BRAF mutations in two cases (7.1%), KIT mutations in three cases (10.7%) and CTNNB1 mutations in one case (3.6%). The BRAF, NRAS and KIT mutation status did not correlate with clinicopathological characteristics. Our results show that KIT, NRAS and BRAF hotspot mutations occur at a low frequency in Korean populations. We also observed a case with the CTNNB1 mutation, which raises the possibility that other pathways are associated with AM development.
authors.affiliation: Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Joon Ho
authors.identifier: 0000-0002-3974-1290
authors.initials: JH
authors.lastname: Shim
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Hyun-Tae
authors.initials: HT
authors.lastname: Shin
authors.affiliation: Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea.
authors.forename: Jiho
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Ji-Hye
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Department of Medical Device Management & Research, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea.
authors.forename: Jong-Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jun-Mo
authors.initials: JM
authors.lastname: Yang
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, Korea.
authors.forename: Duk-Hwan
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Kee-Taek
authors.initials: KT
authors.lastname: Jang
authors.affiliation: Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Dong-Youn
authors.initials: DY
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D019295:Computational Biology; D004252:DNA Mutational Analysis; D005260:Female; D005534:Foot Diseases / Q000235:genetics*; D020558:GTP Phosphohydrolases / Q000235:genetics; D006225:Hand; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D009260:Nail Diseases / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D056910:Republic of Korea; D012463:Saliva; D012878:Skin Neoplasms / Q000235:genetics*; D051176:beta Catenin / Q000235:genetics
chemical_list: C495270:CTNNB1 protein, human; D008565:Membrane Proteins; D051176:beta Catenin; D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
keywords: acral melanoma; mutational profile; next-generation sequencing; β-catenin gene