The Role of SETD2 Gene as an Epigenetic Modifier Factor in Various Cancers

Introduction Accuracy and integration of DNA function in nucleated cells in human bodies, depends on multiple genetic and epigenetic mechanisms. Various epigeneticmechanisms including DNA methylation and histone modification as well as environmental factors affect chromatin structure. In recent years, some progress has been made in understanding of different epigenetic mechanisms. In many cancers, there is a defect in factors which are involved in epigenetic mechanisms. These mechanisms can be targeted in new therapeutic approaches to these diseases. One of these factors is SETD2 gene, a histone methyltransferase that trimethylates lysine 36 of histone H3, and is on the short arm of the chromosome 3 (3p21.31). Our aim is to investigate studies which have been more dealt with the role of SETD2 in different cancers. Material and methodsIn this study, English databases, PubMed and Google scholar were scanned for articles between 2000 and 2015, and relevant articles were selected. Results These studies showed that frequent mutations in SETD2 gene, are related to clear cell renal cell carcinoma (CCRCC) and breast cancer. SETD2 acts as a tumor suppressor and the gene’s mRNA level is higher in noncancerous tissues compared to cancerous tissues. SETD2 has an important role in histone methylation at hTERT’s promoter and telomerase regulation, and disappears in cancers. The evidences indicated the interaction of SETD2 with P53, and proved the role of SETD2 as a tumor suppressor gene again. Genetic changes in SETD2, were identified in pancreatic neuroendocrine tumors. SETD2 has a role in maintaining of genetic integration by nucleosome stabilization, suppression of replication stress and DNA repair. The majority of somatic mutations in this gene, are missense mutations, and this gene is as highly significant in CCRCC and glioblastoma and as near significant in bladder cancers and since SETD2 is necessary for activation of the ATM gene after double strand breaks, its depletion cannot lead to appropriate response to DNA damage by activation of P53. Conclusion SETD2 is a human gene which is responsible for the Histone H3K36 trimethylation. Studies showed that changes in SETD2, have a direct relation with tumorogenesis, because it has a role in transcription elongation and acts as a tumor suppressor. According to this, level of SETD2 transcript is lower in patients’ cancerous tissues, who are in high grade of their disease.

کلیدواژه ها:

SETD2 ، epigenetic ، cancer