N. Adler1,2, C. Mclean2,3, R. Wolfe1, G. McArthur4,5, A. Haydon2,6, T. Tra3, N. Cummings3, V. Mar1,2,7
Introduction: Between 1.2% and 12.7% of patients with melanoma develop multiple primary melanomas (MPM). Knowledge about the somatic mutational diversity in patients with MPM remains limited. This study aimed to determine the frequency and concordance of BRAF and NRAS mutation in tumours arising in patients with MPM.
Methods: Patients with histologically diagnosed MPM who had at least one of their primary melanoma diagnosed at one of three tertiary referral centres in Melbourne, Australia from 2010–2015 were included. Incident and subsequent melanomas underwent mutation testing. Cohen’s kappa (j) coefficient assessed inter-sample agreement between incident and subsequent primary melanomas for BRAF and NRAS mutation status (mutant versus wild-type).
Results: There were 154 MPM patients with 406 primary tumours. 94 patients had two primary melanomas, 41 had three primary melanomas and 19 had four or more primary melanomas. Of 64 patients with mutation testing of at least two primary melanomas, 43 had concordant BRAF wild-type tumours, three had concordant BRAF mutant tumours and 18 had discordant (BRAF mutant/wild-type) mutational status (poor agreement, j=0.10, 95% CI 0.11 to 0.42). Similarly, there was poor agreement for NRAS mutation status between incident and subsequent melanomas (j=0.06, 95% CI 0.10 to 0.57).
Conclusions: Low concordance in BRAF and NRAS mutation status between incident and subsequent melanomas was observed in patients with MPM, highlighting the complexity of accurate molecular classification of these patients. Mutational analysis of metastatic tissue, rather than of a primary melanoma, in patients with MPM should be strongly considered to guide targeted therapy.