Abstract 4341: Large mutational spectrum of cutaneous melanoma in a Brazilian population: The experience of A.C. Camargo Cancer Center
Authors: Macedo Mariana Petaccia de , Fidaldo Felipe , Pinto Clovis Lopes , Duprat João Pedreira , Begnami Maria Dirlei S.f , Carraro Dirce Maria , Cunha Isabela Werneck 
Published: August 2018

Abstract
Introduction: Cutaneous melanoma (CM) is an aggressive type of malignancy, with elevated mortality rates. The Cancer Genome Atlas Network (TCGA) recently reported the molecular classification of CM and divided these lesions according to their somatic mutation profile in 4 categories: BRAF, NRAS or NF1 mutated, and also the triple-negative group. The aim of this study is to describe the spectrum of molecular alterations from a Brazilian population of CM patients.
Methods: DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) tissue from primary and metastatic melanoma samples from A.C. Camargo Cancer Center molecular pathology section. Next-generation sequencing (Ion Torrent®) targeting a 14-gene panel was performed, targeting the following genes: BRAF (códon 600), NRAS (códons 12, 13, 61, 117 and 146) e KIT (éxon 11, 13, 17), KRAS, CTNNB1, IDH1, EGFR, HRAS, PDGFR-a, PIK3CA, RET, JAK2, MET, and CDH1.
Results: 131 cutaneous melanoma samples from different patients were sequenced. The majority of the samples (57%) showed mutation in at least one gene. BRAF was the most frequent detected mutation, found in 40% of the cases, and p.V600E, p.V600K and p.V600R represented 90%, 8% and 2% of BRAF mutations, respectively. NRAS mutation was detected in 10% of the cases, and among those 88% involved codon 61. KIT mutation was identified in 10% of the cases. Mutations in KRAS, CTNNB1, PDGFRa, PIK3CA, EGFR and HRAS were identified in 5%, 4%, 4%, 3%, 2% and 1% of the cases, respectively. No mutations in IDH1, JAK2, MET or RET was identified. Most of the mutated cases showed mutation in only one tested gene (71%), while 14%, 10% and 5% showed mutations in 2, 3 or 4 genes respectively. None of the cases showed simultaneous mutation involving combinations of BRAF, NRAS or KIT mutations.
Discussion and Conclusion: The BRAF, NRAS and KIT mutation frequency in this population with CM diagnosis is similar to the one described in the world literature for this disease, as well as the distribution of the most frequent mutated regions and specific types of mutations. These results add the mutational spectrum of CM of a large Brazilian cohort to the world literature. Treatment of CM with targeted therapies aiming the MAP-Kinase pathway, and especially blocking BRAF, are a reality in the clinical oncology routine for treating CM patients, but there are still many obstacles in order to fully understand the resistance mechanism and the possibility of drug combinations. Additionally, new targeted agents are under development, such as the ones for NRAS mutated cases, and in this way the understanding of the large mutational spectrum of melanoma is of extreme importance in the clinical scenario.
Citation Format: Mariana Petaccia de Macedo, Felipe Fidaldo, Clovis Lopes Pinto, João Pedreira Duprat, Maria Dirlei S.f Begnami, Dirce Maria Carraro, Isabela Werneck Cunha. Large mutational spectrum of cutaneous melanoma in a Brazilian population: The experience of A.C. Camargo Cancer Center [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4341.