RESUMO
Glioblastomas, also known as glioblastoma multiforme (GBM), are the most aggressive and malignant type of primary brain tumor in adults, exhibiting notable variability at the histopathological, genetic and epigenetic levels. Recently, epigenetic alterations have emerged as a common hallmark of many tumors, including GBM. Considering that a deeper understanding of the epigenetic modifications that occur in GBM may increase the knowledge regarding the tumorigenesis, progression and recurrence of this disease, in this review we discuss the recent major advances in GBM epigenetics research involving histone modification, glioblastoma stem cells, DNA methylation, noncoding RNAs expression, including their main alterations and the use of epigenetic therapy as a valid option for GBM treatment.
Assuntos
Neoplasias Encefálicas/genética , Epigênese Genética , Glioblastoma/genética , Biomarcadores Tumorais/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Regulação Neoplásica da Expressão Gênica , Glioblastoma/metabolismo , Glioblastoma/patologia , HumanosRESUMO
Astrocytic gliomas, which are derived from glial cells, are considered the most common primary neoplasias of the central nervous system (CNS) and are histologically classified as low grade (I and II) or high grade (III and IV). Recent studies have shown that astrocytoma formation is the result of the deregulation of several pathways, including the RB/E2F pathway, which is commonly deregulated in various human cancers via genetic or epigenetic mechanisms. On the basis of the assumption that the study of the mechanisms controlling the INK4/ARF locus can help elucidate the molecular pathogenesis of astrocytic tumors, identify diagnostic and prognostic markers, and help select appropriate clinical treatments, the present study aimed to evaluate and compare methylation patterns using bisulfite sequencing PCR and evaluate the gene expression profile using real-time PCR in the genes CDKN2A, CDKN2B, CDC6, Bmi-1, CCND1, and RB1 in astrocytic tumors. Our results indicate that all the evaluated genes are not methylated independent of the tumor grade. However, the real-time PCR results indicate that these genes undergo progressive deregulation as a function of the tumor grade. In addition, the genes CDKN2A, CDKN2B, and RB1 were underexpressed, whereas CDC6, Bmi-1, and CCND1 were overexpressed; the increase in gene expression was significantly associated with decreased patient survival. Therefore, we propose that the evaluation of the expression levels of the genes involved in the RB/E2F pathway can be used in the monitoring of patients with astrocytomas in clinical practice and for the prognostic indication of disease progression.
Assuntos
Astrocitoma/genética , Neoplasias Encefálicas/genética , Fatores de Transcrição E2F/genética , Regulação Neoplásica da Expressão Gênica/genética , Proteína do Retinoblastoma/genética , Transdução de Sinais/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Astrocitoma/patologia , Neoplasias Encefálicas/patologia , Proteínas de Ciclo Celular/genética , Ciclina D1/genética , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Metilação de DNA/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Complexo Repressor Polycomb 1/genética , Prognóstico , Adulto JovemRESUMO
Gastric cancer is considered one of the most deadly tumors worldwide. Even with the decline in its incidence, the mortality rate of this disease has remained high, mainly due to its late diagnosis and to the lack of precise prognostic markers. The main purpose of this review is to present genetic, epigenetic and proteomic molecular markers that may be used in a diagnostic and prognostic manner and to discuss the pros and cons of each type of marker for improving clinical practice. In this sense, we observed that the use of genetic markers, especially mutations and polymorphisms, should be carefully considered, as they are strongly affected by ethnicity. Proteomic-based markers show promise, but the higher costs of the associated techniques continue to make this approach expensive for routine use. Alternatively, epigenetic markers appear to be very promising, as they can be detected in bodily fluids as well as tissues. However, such markers must be used carefully because epigenetic changes may occur due to environmental factors and aging. Despite the advances in technology and its access, to date, there are few defined biomarkers of prognostic and diagnostic use for gastric tumors. Therefore, the use of a panel of several approaches (genetic, epigenetic and proteomic) should be considered the best alternative for clinical practice.
