Análise do Banco de Dados de Genotipagem Germinativa Do Laboratório Personal Oncologia

Abstract

Cancer is essentially a genetic disease or syndrome since the cell acquires a malignant phenotype because of changes in its DNA, more precisely, mutations or variants in genes that regulate the cell cycle. A series of characteristics such as support for proliferative signaling, evasion of growth suppressors, resistance to cell death, favoring replication and immortality, induction of vascularization, activation of invasion and metastasis, among others, are necessary for a cell to acquire a malignant phenotype and that they have the ability to form malignant tumors. Some variants that favor the development of tumors may appear throughout life, which configures the possibility of manifestations of sporadic cancers. Others, however, can be inherited, called germline variants, which gives individuals the possibility of developing hereditary cancer syndromes. Personal Laboratory, located in Belo Horizonte, Brazil, uses NGS technology for the sequencing of tumor and germinal exomes, to detect genetic variants, with diagnostic and target-specific purposes for drugs already available on the market or in the register. The identified variants are cataloged in the laboratory's database, for future consultations and mutation reviews. This study aimed to analyze the Personal Laboratory germline genotyping database. Was traced a descriptive profile of the bank concerning the main types of cancer, genes, and annotated variants. For this purpose, public databases such as Varsome and Clinvar were consulted, and searches were carried out in specialized literature. It was evaluated the relative frequency of variants, the predominance of some mutations in the analyzed population, the occurrence of Hereditary Multilocus Neoplasia Syndrome (MINAS), as well as the associated genotype and phenotype. Were identified 89 genes in the database, 72 (80.89%) of which are tumor suppressors, 8 (8.98%) oncogenes, and 9 (10.11%) of dual or unknown function. Were identified 569 variants and 537 patients. Were calculated the relative frequency of the variants. Were highlighted the most frequent and the four most frequent cancers in the bank, breast, ovary, colorectal, and pancreas, and the penetrance of the most frequent genes to these tumors. This analysis enabled the identification of 4 patients with the possibility of MINAS Syndrome (Multilocus Inherited Neoplasia Allele Syndrome). Were identified 28 situations of patients with the same variant and different phenotypes. Of the 537 patients in the bank, 324 (60.33%) divided into 21 groups, had different genes and variants, with the same cancer phenotype. It is believed that this combined information will enable future analyzes such as evaluating the clinical utility of the genetic panels, a better understanding of the disease with consequent new forms of prevention, diagnosis, and therapeutic targets that are increasingly individualized and precise.