Testing patterns, patient and tumour characteristics and survival by NRAS and KIT genotype in melanoma

Mistry, Khaylen, Jeffrey, Polly, Levell, Nick j ORCID: https://orcid.org/0000-0003-3393-8305, Kennedy, Oliver, Richardson, Kathryn ORCID: https://orcid.org/0000-0002-0741-8413, Craig, Paul, Bright, Chloe, Taylor, Siobhan, Ragan, John, Karponis, Dimitrios ORCID: https://orcid.org/0000-0002-8847-7537, Pethick, Joanna, Lavelle, Katrina, McRonald, Fiona, Hardy, Steven, Vernon, Sally, Dawe, Robert, Proby, Charlotte, Lorigan, Paul and Venables, Zoe c ORCID: https://orcid.org/0000-0002-9929-2693 (2026) Testing patterns, patient and tumour characteristics and survival by NRAS and KIT genotype in melanoma. Clinical and Experimental Dermatology, 51 (4). pp. 604-611. ISSN 0307-6938

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Abstract

BACKGROUND: NRAS and KIT mutations in melanoma bring implications for prognosis, follow-up, selection into trials and potential future treatment with targeted therapies. The frequency of NRAS/KIT mutations and their association with patient/tumour characteristics and survival is poorly documented. OBJECTIVES: To report national data from England on (i) the frequency of NRAS and KIT mutations, (ii) the association of patient/tumour characteristics with NRAS and KIT mutations, and (iii) the survival of patients with NRAS and KIT mutations. METHODS: This retrospective cohort study identified all new melanomas diagnosed in England from 2016 to 2021 and molecular NRAS/KIT testing using data from the National Disease Registration Service. Multivariate logistic regression determined the association between (i) NRAS and KIT testing and patient/tumour characteristics, and (ii) NRAS genotype and patient/tumour characteristics. Age-standardized net survival (NS) analysed melanoma-specific mortality by NRAS and KIT genotype. RESULTS: Of new melanomas diagnosed, 6.6% (6045/91 415) and 3.0% (2705/91 415) had an NRAS and KIT test registered. The proportion of successfully tested tumours that were NRAS and KIT mutated were 30.8% (1811/5887) and 5.8% (148/2560). East of England NRAS tested the highest proportion of cutaneous tumours (11.2%, 1114/9950) compared with the lowest in the North West (1.4%, 172/12 296). Older patients were more likely to have NRAS mutations [odds ratio (OR) 1.01, 95% confidence interval (CI) 1.01-1.02]. Women (OR 0.81, 95% CI 0.71-0.91) and those with head/neck melanomas (OR 0.37, 95% CI 0.31-0.44) were less likely to have NRAS mutations. There was no significant difference in 5-year NS between all-stage NRAS wildtype (WT) and mutated tumours (WT NS 62.3%, 95% CI 58.9-65.9 vs. mutated NS 58.5%, 95% CI 54.0-63.4). Similarly, there was no significant difference in 5-year NS between KIT WT and mutated tumours (WT NS 50.4%, 95% CI 44.7-57.3 vs. mutated NS 52.1%, 95% CI 37.1-73.2). CONCLUSIONS: This is the largest national dataset on melanoma NRAS and KIT status published to date to the best of our knowledge. Variations in NRAS/KIT testing by geographic/demographic factors drive initiatives to ensure consistent care. NRAS-mutated melanoma had a high incidence, which emphasizes the unmet need to develop therapies and trials for NRAS-mutated melanoma. This study increases our understanding of biomarkers NRAS and KIT and provides a foundation for optimizing melanoma care, contributing to advancements in precision oncology.

Item Type:	Article
Additional Information:	Publisher Copyright: © The Author(s) 2025. Published by Oxford University Press on behalf of British Association of Dermatologists.
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Public Health Faculty of Science > Research Groups > Norwich Epidemiology Centre Faculty of Medicine and Health Sciences > Research Groups > Norwich Epidemiology Centre Faculty of Medicine and Health Sciences > Research Groups > Health Promotion
Related URLs:	https://www.scopus.com/pages/publication... https://academic.oup.com/ced/advance-art...
Depositing User:	LivePure Connector
Date Deposited:	12 Jan 2026 10:30
Last Modified:	18 Jun 2026 20:50
URI:	https://ueaeprints.uea.ac.uk/id/eprint/101583
DOI:	10.1093/ced/llaf543

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