Dados do Trabalho

Título

IDENTIFICATION OF TP53 GENE MUTATIONS IN PATIENTS WITH COLORRECTAL CANCER TREATMENT AT A TERTIARY ONCOLOGY CENTER IN THE WESTERN BRAZILIAN AMAZON

Introdução

Colorectal cancer (CRC) is a serious disease that affects millions of people around the world. Associated risk factors may be genetic predisposition as well as environmental origin. The TP53 gene plays a central role in cellular response, acts as a tumor suppressor gene, and is involved in growth control and cell recognition. Mutations in TP53 are commonly found in tumors and result in the inactivation of the p53 protein.

Objetivo

The aim of the study was to analyze TP53 gene mutations in colorectal cancer tumor samples from patients treated at a tertiary oncology center in the western Brazilian Amazon.

Métodos

It was a descriptive cross-sectional study with 75 patients treated at a tertiary oncology center in the western Brazilian Amazon, which aimed to analyze the presence of mutations in the TP53 gene in samples of colorectal cancer tumors. The patients included in the study, after obtaining free and informed consent, underwent an interview to collect socio-epidemiological data and risk factors. Sample collection took place only upon indication of surgical intervention, given the clinical evolution of the patient, and according to the joint decision of both the doctor and the patient. The identification of mutations in the TP53 gene was carried out through nucleotide sequencing using the Sanger method. This study was approved by the internal review board of the Ethics Committee of the FCECON—approval document # 5.180.654, December 21, 2017. SISGEN- A8C2421.

Resultados

From February to December 2022, 75 participants were included in the study, the age group ranged from 18 to 88 years old and the mean age was 58 years old, 37% of the patients were over 66 years old. About the epidemiological data, the frequency of CCR was higher among female participants 61%, 60% of the patients came from rural areas of the Amazonas State, 39 % from Manaus, the capital city and 1% from other Northern states of Brazil. Regarding the analyzed risk factors, 25% of the participants reported a history of smoking and 39% of alcoholism. Sequencing for analysis of TP53 gene mutations was carried out in the tumor sample of 21 participants, who underwent surgery as treatment. The variation (rs6503048 G > A) located in intron 10 was identified in 4 (19%) of the 21 sequenced samples, with variation from G to A, with G wild type and A being a mutation. This variation is cataloged in ClinVar (NCBI - GenBank) as a benign mutation ClinVar Variation ID: 1269356. Sequencing of 12 samples was also performed to identify the R337H (G>A) mutation, which resulted in all negative samples.

Conclusões

The p53 tumor suppressor transcriptionally regulates a myriad of genes involved in cell cycle control, DNA repair, cell survival and cell metabolism and represents one of the best studied tumorigenesis inhibitors. The literature describes that the TP53 gene has some variations that may favor the appearance of different types of tumors, such as the R337H and rs6503048 G > A mutation. The study of the TP53 tumor suppressor gene enabled the identification of the R337H TP53 mutation, which is characterized by encode a histidine in place of arginine (R337H), in exon 10 of the TP53 gene, in the tetramerization domain of the p53 protein.

Palavras-chave

TP53 GENE, MUTATIONS, COLORECTAL CANCER

Financiador do resumo

Fundação de Amparo a Pesquisa do Estado do Amazonas - FAPEAM - PROGRAMA AMAZÔNIDAS E PROGRAMA PAIC 2022-2023