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Zhou Wang, Professor, Ph. Abstract Small cell lung cancer SCLCa special type of lung cancer, is reputed to carry a poor prognosis. However, genetic and epigenetic changes of SCLC are not well established. Few studies have demonstrated that epigenetic silencing of key tumor suppressor genes TSGs is pivotal to initiation and development of SCLC.
These novel TSGs are potential tumor biomarkers for early diagnosis and prognostic prediction. Moreover, epigenetic promoter methylation of TSGs could be a target of intervention with a wide prospect of clinical application. Accepted for publication Aug 12, Lung cancer includes a group of heterogeneous histological types in terms of clinicopathological features and is commonly classified into two major subgroups, small cell lung cancer SCLC and non-small cell lung cancer NSCLC.
The malignant cells exhibit scarce cytoplasm, molded nuclei and neuroendocrine NE differentiation, as evidenced by expressing a variety of NE substance. But SCLC is also different from carcinoid in aspects of carcinogenesis and pathogenesis. The latest advances in molecular biological technologies have found some mechanisms of malignant neoplasia.
In brief, SCLC cells show the abilities of continuos proliferation, evasion of apoptosis, local invasion and remote metastasis, which is related to silence of tumor suppressor genes TSGs.
Genetic and epigenetic alteration both are responsible for inactivation of TSGs. Epigenetic aberration, one of the earliest and most common phenomena in human malignancies, could lead to abrogation of various TSGs.
Studies about epigenetic alteration could be contributed to increasing the rate of early stage at diagnosis, and therefore, the patients with SCLC could benefit from higher early detection possibilities with good responsiveness to intervention and long-time survival. Expression of TSGs is regulated by the gene promotors, while CpG islands are commonly seen in the up-stream of gene promotor.
The clusters of guanine and cytosine GC are ranged from 0. Almost fifty percent of the genes have the so-called CpG islands in the entire genome.
|Associated Data||Each PCR reaction was performed with a total volume of Annealing temperature of PCR amplification for each gene is list in Table 2.|
About eighty percent of the CpG islands are hyper-methylated and related to repetitive elements in the human DNA. The novel thing is that such CpG islands located at the region of gene promoters are usually un-methylated in normal cells 5.
Methylation of CpG islands at their cytosine 5 position is characterized by gene, tissue and differentiation specificities.
Nevertheless, the mechanisms of gene silence via promoter methylation in transcription level are not fully understood.
Current literatures have reported involved mechanisms as follow: Individual tumor types have their characteristic pattern of acquired aberrant methylation.Sep 18, · Aberrant methylation of gene promoter regions is one of the mechanisms for inactivation of tumor suppressor genes in human malignancies.
In this study, the methylation pattern of 24 tumor suppressor genes was analyzed in 75 samples of ovarian cancer using the methylation-specific multiplex ligation. Methylation profiling of tumor suppressor gene (TSGs) promoters is quickly becoming a powerful diagnostic tool for the early detection, prognosis, and even prediction of clinical response to treatment.
Glioblastoma, the most aggressive and least treatable form of malignant glioma, is the most common human brain tumor.
Although many regions of allelic loss occur in glioblastomas, relatively few tumor suppressor genes have been found mutated at such loci. The methylation status of MGMT has.
Keywords: Hepatocellular carcinoma, DNA methylation, Histone modification, Tumor suppressor gene, Gene expression Introduction Hepatocellular carcinoma (HCC) is one of the most common human cancers worldwide, and it is the second leading cause of cancer-related death in China.
The novel methylation targets we identified in CTCL include the putative tumor suppressor genes BCL7a (B-cell CLL/Lymphoma 7a), PTPRG (protein tyrosine phosphatase receptor gamma), and THBS4 (thrombospondin 4).
Another previous study detected methylation of the p16 INK4a tumor suppressor gene by a methylation-sensitive restriction enzyme site-based assay in 6 of 10 matched plasma DNA from invasive breast cancer patients.
There are several potential approaches .