Comparison of Aberrant Methylation of CpG Islands in the p16/CDKN2A and p14/ARF Promoters in Non-Small Cell Lung Cancer and Acute Lymphoblastic Leukemia

Zemlyakova, V. V.; Стрельников, В. В.; Zborovskaya, I. B.; Balukova, O. V.; Майорова, О. А.; Васильев, Е. В.; Zaletaev, D. V.; Немцова, М. В.

doi:10.1023/b:mbil.0000049856.44664.20

Cited by 8 publications

(6 citation statements)

References 14 publications

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“…The presence of a faint but clearly visible band considered as a positive result for methylation of small amounts of alleles in the DNA sample was noted by other researchers [12][13][14], who used methylationsensitive PCR or methylation-specific PCR assay. The obtained data point to a high sensitivity of the method used.…”

Section: Discussionmentioning

confidence: 76%

“…One of the main mechanisms of gene inactivation is aberrant methylation of cytosines in CGIs associated with active promoters. In particular, hypermethylation CGIs of genes involved in carcinogenesis (tumor--suppressor genes and a number of other genes) leads to transcriptional repression and is revealed in cells of different malignant tumors [12][13][14][15]. At the same time, chronic X-ray irradiation (50 cGy, 10 days) of mice also induced hypermethylation of the p16 tumor-supressor gene in the cells of the liver in a sex-specific manner [9].…”

Section: Introductionmentioning

confidence: 99%

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The study of hypermethylation in blood leukocytes of irradiated parents and their children

et al. 2014

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Background: Accumulation of evidence about the epigenetic regulation of genome function suggests the necessity to explore new aspects of the genotoxic action of radiation on the human body. Methodology: A methylation-sensitive PCR assay was used to analyze promoter methylation of p16/CDKN2A, p14/ARF, RASSF1A and GSTP1 genes in blood leukocytes from 103 unirradiated volunteers and 104 irradiated subjects (83 Chernobyl Nuclear Power Plant liquidators and 21 nuclear specialists). Additionally, 21 families whose fathers were nuclear specialists were examined. Results: A significantly elevated frequency of individuals with abnormal methylation of p16/CDKN2A and GSTP1 genes was revealed in the exposed group compared to the control group (p = 0.0097 and p = 0.005, respectively). The occurrence of promoter methylation of RASSF1A gene significantly correlated with aging both in the control group (r = 0, 213; p = 0.006) and in the exposed individuals (r = 0, 212; p = 0,031). No methylated genes were found in the offspring of control families. Conclusion: Our study showed for the fist time that prolonged radiation exposure at low and medium doses is associated with hypermethylation of genes involved in the basic protective functions of cells; an effect that is persistent in blood leukocytes for significant periods after irradiation.

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Section: Discussionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

The study of hypermethylation in blood leukocytes of irradiated parents and their children

et al. 2014

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“…We selected genes and genomic regions based on genomewide methylation profiles we have performed in seven of these 61 patients, and focused on novel or infrequently reported genes. As a reference, we used CDKN2A and RASSF1, which have been frequently reported as being methylated in NSCLC 14,41,42,44 When using band counts, we found that the methylation status of CDKN2A and PARP15 were unable to differentiate between control lung and tumor samples, although we observed a much lower methylation level in control lung samples than in the tumors. CDKN2A hypermethylation is known as an early event in carcinogenesis; 14,21 therefore, tissues that seem histologically normal may already present early cellular transformations that will eventually lead to oncogenesis.…”

Section: Discussionmentioning

confidence: 87%

Genomewide DNA Methylation Analysis Identifies Novel Methylated Genes in Non–Small-Cell Lung Carcinomas

Carvalho

Hou

Haberle

et al. 2013

Journal of Thoracic Oncology

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“…Loss of heterozygosity (LOH) analysis of the BIN1 region was performed with two introgenic and one closely adjacent extragenic microsatellite markers (table 1). Methylation sensitive PCR (MSe-PCR) and methylation specific sequencing protocols were described previously [8]; corresponding primer sets used in this study are listed in table 1 and their relative positions are depicted in Fig. 1.…”

Section: Methodsmentioning

confidence: 99%

Methylation of the BIN1 gene promoter CpG island associated with breast and prostate cancer

Kuznetsova¹,

Кекеева²,

Larin³

et al. 2007

J Carcinog

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BackgroundLoss of BIN1 tumor suppressor expression is abundant in human cancer and its frequency exceeds that of genetic alterations, suggesting the role of epigenetic regulators (DNA methylation). BIN1 re-expression in the DU145 prostate cancer cell line after 5-aza-2'-deoxycytidine treatment was recently reported but no methylation of the BIN1 promoter CpG island was found in DU145.MethodsMethylation-sensitive arbitrarily-primed PCR was used to detect genomic loci abnormally methylated in breast cancer. BIN1 CpG island fragment was identified among the differentially methylated loci as a result of direct sequencing of the methylation-sensitive arbitrarily-primed PCR product and subsequent BLAST alliance. BIN1 CpG island cancer related methylation in breast and prostate cancers was confirmed by bisulphite sequencing and its methylation frequency was evaluated by methylation sensitive PCR. Loss of heterozygosity analysis of the BIN1 region was performed with two introgenic and one closely adjacent extragenic microsatellite markers.BIN1 expression was evaluated by real-time RT-PCR.ResultsWe have identified a 3'-part of BIN1 promoter CpG island among the genomic loci abnormally methylated in breast cancer. The fragment proved to be methylated in 18/99 (18%) and 4/46 (9%) breast and prostate tumors, correspondingly, as well as in MCF7 and T47D breast cancer cell lines, but was never methylated in normal tissues and lymphocytes as well as in DU145 and LNCaP prostate cancer cell lines. The 5'-part of the CpG island revealed no methylation in all samples tested. BIN1 expression losses were detected in MCF7 and T47D cells and were characteristic of primary breast tumors (10/13; 77%), while loss of heterozygosity was a rare event in tissue samples (2/22 informative cases; 9%) and was ruled out for MCF7.ConclusionBIN1 promoter CpG island is composed of two parts differing drastically in the methylation patterns in cancer. This appears to be a common feature of cancer related genes and demands further functional significance exploration. Although we have found no evidence of the functional role of such a non-core methylation in BIN1 expression regulation, our data do not altogether rule this possibility out.

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Comparison of Aberrant Methylation of CpG Islands in the p16/CDKN2A and p14/ARF Promoters in Non-Small Cell Lung Cancer and Acute Lymphoblastic Leukemia

Cited by 8 publications

References 14 publications

The study of hypermethylation in blood leukocytes of irradiated parents and their children

The study of hypermethylation in blood leukocytes of irradiated parents and their children

Genomewide DNA Methylation Analysis Identifies Novel Methylated Genes in Non–Small-Cell Lung Carcinomas

Methylation of the BIN1 gene promoter CpG island associated with breast and prostate cancer

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