Abstract
Abstract Melanoma is the most aggressive form of skin cancer with increasing prevalence in Brazil. The comprehensive molecular profiling of these tumors and the recent genomic classification has improved the knowledge of melanoma biology and foster the identification of potential clinical biomarkers. The aim of this project, as part of the International Cancer Genome Consortium (ICGC) is to perform a genomic profile by whole genome sequencing (WGS) of Brazilian melanomas patients. We reported the WGS using Illumina paired-end sequencing strategy (>30 X-fold coverage) of 66 cases (45% primary and 55% metastatic) and respective matched normal. Overall we observed an average of 46K mutations/genome. The most frequent type of substitutions identified were: C>T (22.5%), T>C (6.4%), T>G (4.4%), T>A (2.9%), C>A (2.8%) and C>G (1.7%). A significative difference between frequency of C>T substitutions was observed among histological subtypes, i.e., acral lentiginous (11.3%), nodular (31.2%) and superficial spreading (25.9%). Among the classic genes involved in melanoma biology, we found that 31.8% of patients had BRAF mutations, being the V600E the most frequent (82.6%). A total of 6.1% of patients had NRAS, 3.0% showed KRAS, one case (1.5%) showed HRAS, and 12.1% showed NF1 mutations. TERT promoter mutation (C250T) was found in 28.8% of patients. TP53 mutations found 4.5% and RB1 in 1.5% of cases. Oncogenic KIT and PDGFRA mutations were observed in 6.1%and 1.5%, respectively. BRAF, NRAS, HRAS, KRAS and NF1 mutation were mutually exclusive. BRAF and TERT mutations were significantly more frequent in superficial than acral lentiginous melanomas. We showed that Brazilian melanoma patients exhibit a high number of single mutations and a similar mutation profile to the one reported in other populations. Acral/lentiginous melanoma subtype, which is a common subtype in our setting, showed a distinct mutation frequency. Further analysis will extend to other relevant genes and will also include the study of additional genomes to reach the goal of genomic landscape of 100 Brazilian melanomas cases. Citation Format: Vinicius L. Vazquez, Adriane Evangelista, Henrique C. Silveira, Camila Crovador, Andre L. Carvalho, Cristovam Scapulatempo-Neto, Jin Lee, Gilles Landman, Joao P. Kitagima, Rui M. Reis. Brazilian melanoma genome project: mutational landscape based on whole-genome sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3386. doi:10.1158/1538-7445.AM2017-3386
Published Version
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