CpG island methylation of TMS1/ASC and CASP8 genes in cervical cancer

<p>Abstract</p> <p>Background</p> <p>Gene silencing associated with aberrant methylation of promoter region CpG islands is an acquired epigenetic alteration that serves as an alternative to genetic defects in the inactivation of tumor suppressor and other genes in human cancers.</p> <p>Aims</p> <p>This study describes the methylation status of <it>TMS1</it>/<it>ASC </it>and <it>CASP8 </it>genes in cervical cancer. We also examined the prevalence of <it>TMS1</it>/<it>ASC </it>and <it>CASP8 </it>genes methylation in cervical cancer tissue and none - neo plastic samples in an effort to correlate with smoking habit and clinicopathological features.</p> <p>Method</p> <p>Target DNA was modified by sodium bisulfite, converting all unmethylated, but not methylated, cytosines to uracil, and subsequently amplified by Methylation Specific (MS) PCR with primers specific for methylated versus unmethylated DNA. The PCR product was detected by gel electrophoresis and combined with the clinical records of patients.</p> <p>Results</p> <p>The methylation pattern of the <it>TMS1</it>/<it>ASC </it>and <it>CASP8 </it>genes in specimens of cervical cancer and adjacent normal tissues were detected [5/80 (6.2%), 3/80 (3.75%)-2/80 (2.5%), 1/80 (1.2%) respectively]. No statistical differences were seen in the extent of differentiation, invasion, pathological type and smoking habit between the methylated and unmethylated tissues (<it>P </it>> 0.05).</p> <p>Conclusion</p> <p>The present study conclude that the frequency of <it>TMS1</it>/<it>ASC </it>and <it>CASP8 </it>genes methylation in cervical cancer are rare (< 6%), and have no any critical role in development of cervical cancer.</p

Role of DNA methylation in head and neck cancer

Head and neck cancer (HNC) is a heterogenous and complex entity including diverse anatomical sites and a variety of tumor types displaying unique characteristics and different etilogies. Both environmental and genetic factors play a role in the development of the disease, but the underlying mechanism is still far from clear. Previous studies suggest that alterations in the genes acting in cellular signal pathways may contribute to head and neck carcinogenesis. In cancer, DNA methylation patterns display specific aberrations even in the early and precancerous stages and may confer susceptibility to further genetic or epigenetic changes. Silencing of the genes by hypermethylation or induction of oncogenes by promoter hypomethylation are frequent mechanisms in different types of cancer and achieve increasing diagnostic and therapeutic importance since the changes are reversible. Therefore, methylation analysis may provide promising clinical applications, including the development of new biomarkers and prediction of the therapeutic response or prognosis. In this review, we aimed to analyze the available information indicating a role for the epigenetic changes in HNC

Genome-wide DNA methylation analysis of human brain tissue from schizophrenia patients

Recent studies suggest that genetic and environmental factors do not account for all the schizophrenia risk and epigenetics also plays a role in disease susceptibility. DNA methylation is a heritable epigenetic modification that can regulate gene expression. Genome-Wide DNA methylation analysis was performed on post-mortem human brain tissue from 24 patients with schizophrenia and 24 unaffected controls. DNA methylation was assessed at over 485 000 CpG sites using the Illumina Infinium Human Methylation450 Bead Chip. After adjusting for age and post-mortem interval (PMI), 4 641 probes corresponding to 2 929 unique genes were found to be differentially methylated. Of those genes, 1 291 were located in a CpG island and 817 were in a promoter region. These include NOS1, AKT1, DTNBP1, DNMT1, PPP3CC and SOX10 which have previously been associated with schizophrenia. More than 100 of these genes overlap with a previous DNA methylation study of peripheral blood from schizophrenia patients in which 27 000 CpG sites were analysed. Unsupervised clustering analysis of the top 3 000 most variable probes revealed two distinct groups with significantly more people with schizophrenia in cluster one compared to controls (p = 1.74x10-4). The first cluster was composed of 88% of patients with schizophrenia and only 12% controls while the second cluster was composed of 27% of patients with schizophrenia and 73% controls. These results strongly suggest that differential DNA methylation is important in schizophrenia etiology and add support for the use of DNA methylation profiles as a future prognostic indicator of schizophrenia

Analysis of p15ⁱⁿᵏ⁴ᵇ and p16ⁱⁿᵏ⁴ᵃ gene methylation in patients with oral squamous cell carcinoma

[Extract] Cancer is the third leading cause of death in Iran, after coronary heart disease and accidents (Mousavi and Somi 2009). Apart from alterations in the various cellular oncogenes, dysregulation of tumour suppressor genes is an important event in the pathogenesis of cancer. Tumor suppressor genes, especially those involved in call cycle regulation, are inactivated frequently in a variety of cancers (Cunningham and Roussel 2001). Two closely linked tumor suppressor genes, p15ⁱⁿᵏ⁴ᵇ and p16ⁱⁿᵏ⁴ᵃ, are located at chromosome 9p21; they encode their respective cyclin-dependent kinase inhibitors (CDKI)- p15ⁱⁿᵏ⁴ᵇ and p16ⁱⁿᵏ⁴ᵃ