title: NRAS and EPHB6 mutation rates differ in metastatic melanomas of patients in the North Island versus South Island of New Zealand.
abstract: Melanoma, the most aggressive skin cancer type, is responsible for 75% of skin cancer related deaths worldwide. Given that New Zealand (NZ) has the world's highest melanoma incidence, we sought to determine the frequency of mutations in NZ melanomas in recurrently mutated genes. NZ melanomas were from localities distributed between North (35°S-42°S) and South Islands (41°S-47°S). A total of 529 melanomas were analyzed for BRAF exon 15 mutations by Sanger sequencing, and also by Sequenom MelaCarta MassARRAY. While, a relatively low incidence of BRAFV600E mutations (23.4%) was observed overall in NZ melanomas, the incidence of NRAS mutations in South Island melanomas was high compared to North Island melanomas (38.3% vs. 21.9%, P=0.0005), and to The Cancer Genome Atlas database (TCGA) (38.3% vs. 22%, P=0.0004). In contrast, the incidence of EPHB6G404S mutations was 0% in South Island melanomas, and was 7.8% in North Island (P=0.0002). Overall, these data suggest that melanomas from geographically different regions in NZ have markedly different mutation frequencies, in particular in the NRAS and EPHB6 genes, when compared to TCGA or other populations. These data have implications for the causation and treatment of malignant melanoma in NZ.
authors.affiliation: Capital and Coast District Health Board, Wellington, New Zealand.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Jones
authors.affiliation: Capital and Coast District Health Board, Wellington, New Zealand.|Department of Pathology and Molecular Medicine, Wellington School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand.
authors.forename: Peter
authors.initials: P
authors.lastname: Ferguson
authors.affiliation: Anatomical and Molecular Pathology, Canterbury Health Laboratories, Christchurch, New Zealand.
authors.forename: Jacqui
authors.initials: J
authors.lastname: Gardner
authors.affiliation: Capital and Coast District Health Board, Wellington, New Zealand.
authors.forename: Serena
authors.initials: S
authors.lastname: Rooker
authors.affiliation: Pathlab Bay of Plenty, Tauranga, New Zealand.
authors.forename: Tim
authors.initials: T
authors.lastname: Sutton
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ahn
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.|Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand.
authors.forename: Aniruddha
authors.initials: A
authors.lastname: Chatterjee
authors.affiliation: Anatomical and Molecular Pathology, Canterbury Health Laboratories, Christchurch, New Zealand.
authors.forename: Vivienne M
authors.initials: VM
authors.lastname: Bickley
authors.affiliation: Department of Obstetrics and Gynaecology, Christchurch School of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: Makhdoom
authors.initials: M
authors.lastname: Sarwar
authors.affiliation: Anatomic Pathology Services, Auckland District Health Board, New Zealand.|Department of Pathology and Molecular medicine, University of Auckland, Auckland, New Zealand.
authors.forename: Patrick
authors.initials: P
authors.lastname: Emanuel
authors.affiliation: Capital and Coast District Health Board, Wellington, New Zealand.|Department of Pathology and Molecular Medicine, Wellington School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand.
authors.forename: Diane
authors.initials: D
authors.lastname: Kenwright
authors.affiliation: Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand.|Department of Pathology and Molecular medicine, University of Auckland, Auckland, New Zealand.
authors.forename: Peter R
authors.initials: PR
authors.lastname: Shepherd
authors.affiliation: Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.|Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Eccles
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics*; D005843:Geography; D006801:Humans; D015994:Incidence; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D059645:Mutation Rate; D009362:Neoplasm Metastasis; D009520:New Zealand / Q000453:epidemiology; D036081:Receptors, Eph Family / Q000235:genetics*; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D055815:Young Adult; D000096142:Cutaneous Malignant Melanoma
chemical_list: D008565:Membrane Proteins; C106797:EPHB6 protein, human; D036081:Receptors, Eph Family; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
keywords: BRAF; EPHB6; NRAS; melanoma; mutations