Mutation analysis of mucosal and cutaneous melanomas during progression.

Abstract

e21047 Background: The prevalence of mutations in driver genes during progression in cutaneous and mucosal melanomas remains inconclusive. We investigated the prevalence and distribution of mutations in main candidate genes involved in melanomagenesis among different melanoma tissues using a next-generation sequencing (NGS) approach. Methods: Forty-eight tumor samples from 36 patients with mucosal melanoma (MM) and fifty-two tumor samples from 34 patients with cutaneous melanoma (CM) were collected, after obtaining patients’ written informed consent for tissue sampling. Genomic DNA was isolated from macrodissected tumor tissues containing at least 80% neoplastic cells and analyzed for mutations in 25 most common melanoma-associated oncogenes and tumor suppressor genes, using the IMI Diagnostic Melanoma Panel on the Ion Torrent platform (Life Technologies, USA). Results: A total of 100 tumor tissues from 70 melanoma patients were analyzed. BRAF mutations were detected in 21/34 (62%) CM patients and 13/36 (36%) mm patients. The second most prevalent mutations were found in K-/N-RAS (6/34; 18%) and cKIT (6/36; 17%) genes among CM and mm patients, respectively. No concomitant mutations of BRAF, RAS, and cKIT genes were detected. Among others, mutations were more frequently found in CCND1 (20%), ARID2 (16%), and NF1(12%) genes, considering the entire series of patients. Vast majority of patients who had paired samples of primary and secondary melanomas showed consistent mutation patterns between primary tumors and metastatic lesions. Similar frequencies of mutations in driver genes were seen across metastatic sites. Conclusions: In the era of targeted therapies, assessment of the spectrum and distribution of mutations in main molecular targets among patients with melanoma is needed. Our findings about the prevalence of mutations in driver genes in paired tumor lesions from patients with cutaneous and mucosal melanoma may be useful in the management of such diseases. The Italian Melanoma Intergroup (IMI) includes the following additional members who participated as investigators in this study: Mario Mandalà, Paola Queirolo, Ignazio Stanganelli, Vanna Chiarion Sileni, Pietro Quaglino, Anna Maria Di Giacomo.