Somatic mutation profile of a panel of oncogenes and tumor suppressor genes in colorectal cancer in a Brazilian population.

Abstract Colorectal cancer (CRC) is the third most frequent cancer worldwide and the fourth leading cause of death due to cancer. The development of this disease usually occurs due to the progression of precursor lesions in the normal intestinal mucosa to tumor. Environment, age, lifestyle, and genetic background are considered risk factors for the development and progression of CRC. The molecular abnormalities involved in the progression of CRC have been well characterized, including mutations, microsatellite instability, and epigenetic changes. Although the molecular profile of colorectal cancer is well known in developed countries, in the Brazilian population information is still very limited. Therefore, in the present study we intended to characterize the mutation profile of a Brazilian population and associate this with their clinicopathologic features. A total of 61 colorectal cancer cases of different stages were included. DNA was extracted from frozen fresh tumors and sequenced using a panel of 298 genes by next-generation sequencing (NGS). The mean age of patients was 63 years old; 57.4% were male. Three patients had CRC in stage 0, 16 in stage I, 29 in stage II, 10 in stage III, and three in stage IV. Considering only nonsynonymous alterations, we found on average 7.24 mutations per patient. The majority were missense (61.8%), followed by nonsense (15.2%) and frameshift mutations (10.9%). The genes most frequently mutated were APC (78.7%), TP53 (72.1%), KRAS (60.7%), PIK3CA (14.8%), and FBXW7 (14.8%). Alterations in tumor suppressor genes such as APC and TP53 were found throughout the entire gene. On the other hand, oncogenes such as KRAS had alterations in hotspots of the gene. In conclusion, the frequency of alterations in genes sequenced in our population was similar to that found in the international literature for other populations. Citation Format: Wellington Santos, Adriane Feijó Evangelista, Ronilson Durães, Marcus Matsushita, Rui Manuel Reis, Denise Peixoto Guimarães. Somatic mutation profile of a panel of oncogenes and tumor suppressor genes in colorectal cancer in a Brazilian population [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr A35.