Methylation Status of RB1 Promoter in Indian Retinoblastoma Patients

Joseph, Biju; Mamatha, Gandra; Raman, Gayathree; Shanmugam, Mahesh Palanivelu; Kumaramanickavel, Govindasamy

doi:10.4161/cbt.3.2.620

Cited by 14 publications

(5 citation statements)

References 19 publications

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“…Methylation-mediated blocking of activation of RB promoter may reduce RB expression to 8.0% in vitro (OhtaniFujita et al, 1993). CGIs at 5 0 end of the RB gene were found hypermethylated in NSCLC (Joseph et al, 2004). Aberrant methylation of TGFBR2, a major inhibitor of epithelial cell growth and functions as TSG, may be associated with down-regulation of TGFBR2 expression at the transcriptional level in NSCLC (Zhang et al, 2004).…”

Section: Hypermethylation and Hypomethylation In Lung Cancermentioning

confidence: 92%

DNA Methylation and Nonsmall Cell Lung Cancer

Lü

Zhang

2011

The Anatomical Record

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Lung cancer is the leading cause of cancer-related death in men and women worldwide. Owing to the scarcity of effective tools for early detection and therapy strategies, the 5-year survival rate of lung cancer is very poor. Because the accumulation of multiple genetic and/or epigenetic changes, including DNA methylation, has been suggested to contribute to development and progression of human cancers, improved understanding of the relationship between DNA methylation and lung cancer will provide new insights for identifying promising biomarkers for diagnosis, prognosis, and treatment of lung cancer. Here, we present a relatively comprehensive review of DNA methylation and lung cancer, discuss DNA methylation changes in carcinogenesis and metastasis of lung cancer, and explore the association of microRNA with DNA methylation. Additionally, we outline the applications of DNA methylation in clinical practice, such as diagnosis, prognosis, and therapy of lung cancer. Anat Rec, 294:1787Rec, 294: -1795Rec, 294: , 2011. V V C 2011 Wiley-Liss, Inc.

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Section: Hypermethylation and Hypomethylation In Lung Cancermentioning

confidence: 92%

DNA Methylation and Nonsmall Cell Lung Cancer

Lü

Zhang

2011

The Anatomical Record

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“…And in fact, gross deletion or duplication, promoter methylation of the RB1 gene and MYCN amplification without RB1 mutation have been identified in RB tumors [2, 4, 7, 10, 14, 16, 17]. The aim of the current study was to understand the incidence of retinoblastoma in Guatemala and the nature of the RB1 mutations in patients with this intraocular tumor.…”

Section: Introductionmentioning

confidence: 98%

Increased incidence and disparity of diagnosis of retinoblastoma patients in Guatemala

Dean

Bendfeldt

et al. 2014

Cancer Letters

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Analysis of 327 consecutive cases at a pediatric referral hospital of Guatemala reveals that retinoblastoma accounts for 9.4% of all cancers and the estimated incidence is 7.0 cases/million children, higher than the United States or Europe. The number of familial cases is low, and there is a striking disparity in indigenous children due to late diagnosis, advanced disease, rapid progression and elevated mortality. Nine germline mutations in 18 patients were found; two known and five new mutations. Hypermethylation of RB1 was identified in 13% of the tumors. An early diagnosis program could identify cases at an earlier age and improve outcome of retinoblastoma in this diverse population.

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“…With the aim of better understanding the mechanisms associated with Rb promoter epigenetic silencing, we analyzed its DNA methylation status in detail in different cell types [13-16]. We asked whether the absence of CTCF binding to the Rb promoter is able to contribute, firstly, to more rapid and extensive DNA methylation, and secondly, to faster and robust epigenetic silencing.…”

Section: Introductionmentioning

confidence: 99%

Gain of DNA methylation is enhanced in the absence of CTCF at the human retinoblastoma gene promoter

et al. 2011

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BackgroundLong-term gene silencing throughout cell division is generally achieved by DNA methylation and other epigenetic processes. Aberrant DNA methylation is now widely recognized to be associated with cancer and other human diseases. Here we addressed the contribution of the multifunctional nuclear factor CTCF to the epigenetic regulation of the human retinoblastoma (Rb) gene promoter in different tumoral cell lines.MethodsTo assess the DNA methylation status of the Rb promoter, genomic DNA from stably transfected human erythroleukemic K562 cells expressing a GFP reporter transgene was transformed with sodium bisulfite, and then PCR-amplified with modified primers and sequenced. Single- and multi-copy integrants with the CTCF binding site mutated were isolated and characterized by Southern blotting. Silenced transgenes were reactivated using 5-aza-2'-deoxycytidine and Trichostatin-A, and their expression was monitored by fluorescent cytometry. Rb gene expression and protein abundance were assessed by RT-PCR and Western blotting in three different glioma cell lines, and DNA methylation of the promoter region was determined by sodium bisulfite sequencing, together with CTCF dissociation and methyl-CpG-binding protein incorporation by chromatin immunoprecipitation assays.ResultsWe found that the inability of CTCF to bind to the Rb promoter causes a dramatic loss of gene expression and a progressive gain of DNA methylation.ConclusionsThis study indicates that CTCF plays an important role in maintaining the Rb promoter in an optimal chromatin configuration. The absence of CTCF induces a rapid epigenetic silencing through a progressive gain of DNA methylation. Consequently, CTCF can now be seen as one of the epigenetic components that allows the proper configuration of tumor suppressor gene promoters. Its aberrant dissociation can then predispose key genes in cancer cells to acquire DNA methylation and epigenetic silencing.

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Methylation Status of RB1 Promoter in Indian Retinoblastoma Patients

Cited by 14 publications

References 19 publications

DNA Methylation and Nonsmall Cell Lung Cancer

DNA Methylation and Nonsmall Cell Lung Cancer

Increased incidence and disparity of diagnosis of retinoblastoma patients in Guatemala

Gain of DNA methylation is enhanced in the absence of CTCF at the human retinoblastoma gene promoter

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