NRAS and EPHB6 mutation rates differ in metastatic melanomas of patients in the North Island versus South Island of New Zealand
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Angela M. Jones1,*, Peter Ferguson1,2,*, Jacqui Gardner3, Serena Rooker1, Tim Sutton4, Antonio Ahn5, Aniruddha Chatterjee5,6, Vivienne M. Bickley3, Makhdoom Sarwar7, Patrick Emanuel8,9, Diane Kenwright1,2, Peter R. Shepherd6,9, Michael R. Eccles5,6
1Capital and Coast District Health Board, Wellington, New Zealand
2Department of Pathology and Molecular Medicine, Wellington School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand
3Anatomical and Molecular Pathology, Canterbury Health Laboratories, Christchurch, New Zealand
4Pathlab Bay of Plenty, Tauranga, New Zealand
5Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand
6Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand
7Department of Obstetrics and Gynaecology, Christchurch School of Medicine, University of Otago, Christchurch, New Zealand
8Anatomic Pathology Services, Auckland District Health Board, New Zealand
9Department of Pathology and Molecular medicine, University of Auckland, Auckland, New Zealand
*These authors contributed equally to this work, and as co-first authors
Michael R. Eccles, email: firstname.lastname@example.org
Keywords: melanoma, mutations, NRAS, BRAF, EPHB6
Received: February 11, 2016 Accepted: April 16, 2016 Published: May 13, 2016
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.
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