Gene-promoter hypermethylation as a biomarker in lung cancer

Belinsky, Steven A.

doi:10.1038/nrc1432

Cited by 484 publications

(412 citation statements)

References 102 publications

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“…An epigenetic alteration might function as a marker prior to the development of cancer [91][92][93]. Thus, epigenetic markers may be crucial for identifying the risk of cancer development.…”

Section: Perspectivesmentioning

confidence: 99%

Epigenetic changes in virus-associated human cancers

Leu

Chang

2005

Cell Res

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Epigenetics of human cancer becomes an area of emerging research direction due to a growing understanding of specific epigenetic pathways and rapid development of detection technologies. Aberrant promoter hypermethylation is a prevalent phenonmena in human cancers. Tumor suppressor genes are often hypermethylated due to the increased activity or deregulation of DNMTs. Increasing evidence also reveals that viral genes are one of the key players in regulating DNA methylation. In this review, we will focus on hypermethylation and tumor suppressor gene silencing and the signal pathways that are involved, particularly in cancers closely associated with the hepatitis B virus, simian virus 40 (SV40), and Epstein-Barr virus. In addition, we will discuss current technologies for genome-wide detection of epigenetically regulated targets, which allow for systematic DNA hypermethylation analysis. The study of epigenetic changes should provide a global view of gene profile in cancer, and epigenetic markers could be used for early detection, prognosis, and therapy of cancer.

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Section: Perspectivesmentioning

confidence: 99%

Epigenetic changes in virus-associated human cancers

Leu

Chang

2005

Cell Res

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“…Aberrant DNA methylation patterns are extremely common in all types of tumors. In considerations of: i) the role of DNA methylation in the regulation of gene expression and in the maintenance of genome stability; ii) the aberrant methylation patterns observed in human specimens ahead of the onset of malignancy [84,85]; iii) the sensitivity of cancer patients to DNMTs and HDACs inhibitors, it is plausible that an epigenetic deregulation in general and altered DNA methylation pattern in particular are not a consequence but rather a primary cause of malignant state [86].…”

Section: Abe Rrant Epigenetic Changes Of Dna and Chromatin In Human Dmentioning

confidence: 99%

Dynamic and reversibility of heterochromatic gene silencing in human disease

et al. 2005

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In eukaryotic organisms cellular fate and tissue specific gene expression are regulated by the activity of proteins known as transcription factors that by interacting with specific DNA sequences direct the activation or repression of target genes. The post genomic era has shown that transcription factors are not the unique key regulators of gene expression. Epigenetic mechanisms such as DNA methylation, post-translational modifications of histone proteins, remodeling of nucleosomes and expression of small regulatory RNAs also contribute to regulation of gene expression, determination of cell and tissue specificity and assurance of inheritance of gene expression levels. The relevant contribution of epigenetic mechanisms to a proper cellular function is highlighted by the effects of their deregulation that cooperate with genetic alterations to the development of various diseases and to the establishment and progression of tumors.

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“…It is also the leading cause of cancer-related deaths worldwide. The global rise in lung cancer incidence, together with poor survival rate (Belinsky, 2004) and refractory to traditional chemotherapy, underscores the magnitude of the lung cancer epidemic and the urgent need for a more thorough understanding of the mechanisms responsible for this malignancy (Schrump and Nguyen, 2005). With this regard, identifications of key molecular targets and cellular pathways involved in pulmonary carcinogenesis would have significant therapeutic implications.…”

Section: Introductionmentioning

confidence: 99%

Cigarette smoke induces demethylation of prometastatic oncogene synuclein-γ in lung cancer cells by downregulation of DNMT3B

et al. 2007

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The prometastatic oncogene synuclein-c (SNCG) is not expressed in normal lung tissues, but it is highly expressed in lung tumors. Here, we show that cigarette smoke extract (CSE) has strong inducing effects on SNCG gene expression in A549 lung cancer cells through demethylation of SNCG CpG island. CSE treatment also augments the invasive capacity of A549 cells in an SNCG-dependent manner. To elucidate the mechanisms underlying the demethylating effects of CSE, we examined expression levels of DNA methyltransferases (DNMTs), 1, 3A and 3B in CSE-treated cells. We show that the mRNA expression of DNMT3B is specifically downregulated by CSE with a kinetics concurrent to SNCG reexpression. Utilizing siRNA to knockdown DNMT3B expression, we show that inhibition of DNMT3B directly increases SNCG mRNA expression. We further show that exogenous overexpression of DNMT3B in an SNCG-positive lung cancer cell line H292 suppresses SNCG mRNA and protein expression and induces de novo methylation of SNCG CpG island, whereas overexpression of DNMT1 or DNMT3A has no effects. Taken together, these new findings demonstrate that tobacco exposure induces the abnormal expression of SNCG in lung cancer cells through downregulation of DNMT3B. This work sheds light on the molecular understanding of demethylation of this oncogene during cancer progression.

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Gene-promoter hypermethylation as a biomarker in lung cancer

Cited by 484 publications

References 102 publications

Epigenetic changes in virus-associated human cancers

Epigenetic changes in virus-associated human cancers

Dynamic and reversibility of heterochromatic gene silencing in human disease

Cigarette smoke induces demethylation of prometastatic oncogene synuclein-γ in lung cancer cells by downregulation of DNMT3B

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