scholarly journals DNA Methylation in Circulating Tumour DNA as a Biomarker for Cancer

2007 ◽  
Vol 2 ◽  
pp. 117727190700200 ◽  
Author(s):  
Ruth E Board ◽  
Lucy Knight ◽  
Alastair Greystoke ◽  
Fiona H Blackhall ◽  
Andrew Hughes ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Primary Tumour ◽  
Predictive Biomarkers ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Potential Biomarker ◽  
Frequent Event ◽  
Promotor Region ◽  
Circulating Tumour Dna

Free circulating DNA, which is thought to be derived from the primary tumour, can be detected in the blood of patients with cancer. Detection of genetic and epigenetic alteration in this tumour DNA offers a potential source of development of prognostic and predictive biomarkers for cancer. One such change is DNA methylation of the promotor region of tumour suppressor genes. This causes down regulation of tumour suppressor gene expression, a frequent event in carcinogenesis. Hypermethylation of the promotor region of a number of genes has been detected in many tumour types and more recently these changes have been detected in circulating tumour DNA. This review will summarise the literature detailing DNA methylation in circulating tumour DNA and discuss some of the current controversies and technical challenges facing its use as a potential biomarker for cancer.

scholarly journals A Label-Free DNA-Immunosensor Based on Aminated rGO Electrode for the Quantification of DNA Methylation

Nanomaterials ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 985
Author(s):  
Mina Safarzadeh ◽  
Ahmed Suhail ◽  
Jagriti Sethi ◽  
Anas Sattar ◽  
David Jenkins ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Photoelectron Spectroscopy ◽  
Electrode Surface ◽  
Dna Methyltransferase ◽  
Limit Of Detection ◽  
Disease Diagnosis ◽  
Tumour Suppressor Gene ◽  
Efficient Production ◽  
Label Free ◽  
Potential Biomarker

In this work, we developed a sandwich DNA-immunosensor for quantification of the methylated tumour suppressor gene O-6-methylguanine-DNA methyltransferase (MGMT), which is a potential biomarker for brain tumours and breast cancer. The biosensor is based on aminated reduced graphene oxide electrode, which is achieved by ammonium hydroxide chemisorption and anti-5-methylcytosine (anti-5mC) as a methylation bioreceptor. The target single-strand (ss) MGMT oligonucleotide is first recognised by its hybridisation with complementary DNA to form double-stranded (ds) MGMT, which is then captured by anti-5mC on the electrode surface due to the presence of methylation. Raman spectroscopy, X-ray photoelectron spectroscopy (XPS) and Scanning electron microscopy (SEM) techniques were used to characterise the electrode surface. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques were used for electrochemical measurements. Under optimised conditions, the proposed biosensor is able to quantify a linear range of concentrations of the MGMT gene from 50 fM to 100 pM with a limit of detection (LOD) of 12 fM. The sandwich design facilitates the simultaneous recognition and quantification of DNA methylation, and the amination significantly improves the sensitivity of the biosensor. This biosensor is label-, bisulfite- and PCR-free and has a simple design for cost-efficient production. It can also be tailor-made to detect other methylated genes, which makes it a promising detection platform for DNA methylation-related disease diagnosis and prognosis.

Use of Monozygotic Twins in Search for Breast Cancer Susceptibility Loci

Twin Research ◽  
2001 ◽  
Vol 4 (4) ◽  
pp. 251-259 ◽  
Author(s):  
Asta Försti ◽  
Qianren Jin ◽  
Lena Sundqvist ◽  
Magnus Söderberg ◽  
Kari Hemminki
Keyword(s):  
Breast Cancer ◽  
Cancer Susceptibility ◽  
Monozygotic Twins ◽  
Monozygotic Twin ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Suppressor Genes ◽  
Twin Model

AbstractWe have used Swedish monozygotic twins concordant for breast cancer to study genetic changes associated with the development of breast cancer. Because loss of heterozygosity (LOH) at a specific genomic region may reflect the presence of a tumour suppressor gene, loss of the same allele in both of the twins concordant for breast cancer may pinpoint a tumour suppressor gene that confers a strong predisposition to breast cancer. DNA samples extracted from the matched tumour and normal tissues of nine twin pairs were analysed for allelic imbalance using a set of microsatellite markers on chromosomes 1, 13, 16 and 17, containing loci with known tumour suppressor genes. The two main regions, where more twin pairs than expected had lost the same allele, were located at 16qtel, including markers D16S393, D16S305 and D16S413, and at 17p13, distal to the p53 locus. Our results show that the monozygotic twin model can be used to suggest candidate regions of potential tumour suppressor genes, even with a limited number of twin pairs.

Molecular profile of nasopharyngeal carcinoma: analysing tumour suppressor gene promoter hypermethylation by multiplex ligation-dependent probe amplification

2017 ◽  
Vol 71 (4) ◽  
pp. 351-359 ◽  
Author(s):  
Marc L Ooft ◽  
Jolique van Ipenburg ◽  
Rob van Loo ◽  
Rick de Jong ◽  
Cathy Moelans ◽  
...  
Keyword(s):  
Treatment Options ◽  
Disease Free Survival ◽  
Promoter Hypermethylation ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor ◽  
Molecular Profile ◽  
Tumour Suppressor Genes ◽  
Suppressor Genes ◽  
Dependent Probe

AimsTo assess differences in methylation profiles, and thus pathogenesis, between Epstein-Barr virus (EBV)-positive and negative nasopharyngeal carcinomas (NPCs). Also, promoter hypermethylation is a common phenomenon in early carcinogenesis to inactivate tumour suppressor genes. Since epigenetic changes are reversible, the therapeutic application of methylation inhibitors could provide treatment options.MethodsWe evaluated promoter hypermethylation profiles of 22 common tumour suppressor genes in 108 NPCs using methylation-specific multiplex ligation-dependent probe amplification. Correlation between methylation, clinicopathological features (including EBV) and survival was examined. Cluster analysis was also performed.ResultsHypermethylation of RASSF1A and ESR1 was significantly more frequent in EBV-positive NPC, while hypermethylation of DAPK1 was more frequent in EBV-negative NPC. In logistic regression, age, with EBV-positive NPC occurring at earlier age, and RASSF1, with RASSF1 hypermethylation being more frequent in EBV-positive NPC, remained significant. In EBV-positive NPC, hypermethylation of RASSF1A predicted worse overall survival (OS) (HR 3.058,95% CI 1.027 to 9.107). In EBV-negative NPC, hypermethylated adenomatous polyposis coli (APC) was a predictor of poor disease-free survival (DFS) (HR 6.868, 95% CI 2.142 to 22.022).ConclusionThere are important epigenetic differences between EBV-negative and EBV-positive NPCs, with EBV-negative NPC having a more similar hypermethylation profile to other head and neck squamous cell carcinomas than EBV-positive NPC. Hypermethylation of RASSF1A might contribute to worse OS in EBV-positive NPC, and may be an important event in the pathogenesis of EBV-infected NPC. Hypermethylation of APC might contribute to worse DFS in EBV-negative NPC.

scholarly journals Is DNA methylation of tumour suppressor genes epigenetic?

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Kevin Struhl
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Cancer Cells ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Suppressor Genes ◽  
Colorectal Cancer Cells ◽  
Transcriptional Pathway

In colorectal cancer cells, a non-epigenetic transcriptional pathway that is mediated by an oncogene maintains DNA methylation of tumour suppressor genes

scholarly journals Association between the TP53 and CYP2E1*5B gene polymorphisms and non-small cell lung cancer

2016 ◽  
Vol 67 (4) ◽  
pp. 311-316 ◽  
Author(s):  
Ahmet Oguz Ada ◽  
Serdar Bilgen ◽  
Volkan Karacaoglan ◽  
Celalettin Semih Kunak ◽  
Emre Soydas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Genetic Polymorphisms ◽  
Cell Lung Cancer ◽  
Gene Polymorphisms ◽  
Tumour Suppressor Gene ◽  
Small Cell ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Small Cell Lung

Abstract Non-small cell lung cancer (NSCLC) is the most common form of lung cancer. Genetic polymorphisms in tumour suppressor genes and genes encoding xenobiotic metabolising enzymes alter the activity of their corresponding enzymes and are important individual susceptibility factors for NSCLC. Because of the lack of information in literature, the aim of our study was to investigate the role of the tumour suppressor gene TP53 (Arg72Pro) and the xenobiotic metabolising CYP2E1*5B gene polymorphisms on the risk of NSCLC development. The study population consisted of 172 patients and 172 controls (156 men and 16 women in each group). Genetic polymorphisms were determined with real-time polymerase chain reaction (PCR) and PCR restriction fragment length polymorphism (PCR-RFLP). Multivariate analysis showed a significant association with NSCLC for the combination between the TP53 codon72 Arg/Pro and the Pro/Pro genotypes (OR 2.21, 95 % CI 1.390-3.51; p=0.001). We also analysed whether combinations of these gene variants with GSTM1, GSTT1, GSTP1 exon 5 (Ile105Val), and GSTP1 exon 6 (Ala114Val) gene polymorphisms were associated with the NSCLC risk. A significant increase in the risk was observed for the following combinations: TP53 codon72 variant with GSTM1 null (OR 2.22, 95 % CI 1.23-4.04; p=0.009), GSTT1 null (OR 2.98, 95 % CI 1.49-5.94; p=0.002), and GSTP1 (Ala114Val) variant genotypes (OR 3.38, 95 % CI 1.54-7.41; p=0.002). Further studies with larger samples are needed to verify these findings.

Folic acid enforces DNA methylation-mediated transcriptional silencing of PTEN, APC and RARbeta2 tumour suppressor genes in breast cancer

2013 ◽  
Vol 430 (2) ◽  
pp. 623-628 ◽  
Author(s):  
Katarzyna Lubecka-Pietruszewska ◽  
Agnieszka Kaufman-Szymczyk ◽  
Barbara Stefanska ◽  
Krystyna Fabianowska-Majewska
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Folic Acid ◽  
Transcriptional Silencing ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Suppressor Genes

scholarly journals PTEN regulates glioblastoma oncogenesis through chromatin-associated complexes of DAXX and histone H3.3

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Jorge A. Benitez ◽  
Jianhui Ma ◽  
Matteo D’Antonio ◽  
Antonia Boyer ◽  
Maria Fernanda Camargo ◽  
...  
Keyword(s):  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor ◽  
Growth Defect ◽  
Tumour Suppressor Genes ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Pten Deletion ◽  
Therapeutic Opportunity ◽  
Associated Function

Abstract Glioblastoma (GBM) is the most lethal type of human brain cancer, where deletions and mutations in the tumour suppressor gene PTEN (phosphatase and tensin homolog) are frequent events and are associated with therapeutic resistance. Herein, we report a novel chromatin-associated function of PTEN in complex with the histone chaperone DAXX and the histone variant H3.3. We show that PTEN interacts with DAXX and, in turn PTEN directly regulates oncogene expression by modulating DAXX-H3.3 association on the chromatin, independently of PTEN enzymatic activity. Furthermore, DAXX inhibition specifically suppresses tumour growth and improves the survival of orthotopically engrafted mice implanted with human PTEN-deficient glioma samples, associated with global H3.3 genomic distribution changes leading to upregulation of tumour suppressor genes and downregulation of oncogenes. Moreover, DAXX expression anti-correlates with PTEN expression in GBM patient samples. Since loss of chromosome 10 and PTEN are common events in cancer, this synthetic growth defect mediated by DAXX suppression represents a therapeutic opportunity to inhibit tumorigenesis specifically in the context of PTEN deletion.

scholarly journals Non-accidental structural chromosome aberrations in established monkey B-lymphocyte cell lines

Biologija ◽  
2020 ◽  
Vol 65 (4) ◽  
Author(s):  
Daredzhan Araviashvili ◽  
Olga Chzhu ◽  
Igor Marinich ◽  
Irina Danilova
Keyword(s):  
Cell Lines ◽  
Chromosomal Aberrations ◽  
Suppressor Gene ◽  
Tumour Suppressor Gene ◽  
Tumour Suppressor ◽  
Chromosome 8 ◽  
Tumour Suppressor Genes ◽  
Suppressor Genes ◽  
Cultivation In Vitro ◽  
Lymphocyte Cell

Established primate lymphocyte cell lines obtained from tumour samples and from EBV-positive monkeys served us as the model system for studying the role of genetic factors and chromosomal abnormalities in malignization. The investigation of chromosome regions and genes involved in chromosomal aberrations leading to malignization in these lines was the aim of our work. Cytogenetic analysis was performed at different stages of cultivation in vitro. To determine the oncogenes and tumour suppressor genes located on aberrant chromosomes, data on mapping rhesus macaque genes, and high similarity of human and monkey karyotypes were used. We found that, in the line obtained from lymphomatous baboon tissue, the inactivation of tumour suppressor gene RB1 on chromosome 17 after chromosomal rearrangement is one of the most probable causes of in vivo malignization. Chromosomal aberrations at the region of oncogene c-Ki-ras and tumour suppressor gene TP53 change the proliferative status and differentiation in established cell lines obtained from healthy but EBV-seropositive primates. The other cause of malignization in these lines is an increase in expression of the oncogene c-myc caused by trisomy of chromosome 8 where c-myc is located. Structural aberrations in established primate cell lines affecting several chromosomal loci were identified as: (1) causing the proto-oncogene activation – the central event in the tumour clone occurrence, and (2) deactivating tumour suppressor genes. The change in the chromosome number leads to increase in oncogenic products and to damage of regulatory functions associated with cell proliferation.

scholarly journals Hypermethylation involved in DNA profiles of lung cancer specific tumour suppressor genes and epigenetic modification caused by an ultra-highly diluted homeopathic drug, Condurango 30C, in vitro and in vivo

2021 ◽  
Vol 13 (47) ◽  
pp. 99-99
Author(s):  
Anisur Rahman Khuda-Bukhsh ◽  
Sourav Sidkar
Keyword(s):  
Lung Cancer ◽  
Dna Methylation ◽  
Epigenetic Modification ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Dna Hypermethylation ◽  
Suppressor Genes ◽  
Homeopathic Drug

Background and objectives: DNA hyper-methylation is an important aspect involved in carcinogenesis and cancer progression, which affects mainly CpG islands of DNA and causes inactivation of tumour suppressor genes. Therefore DNA hypermethylation status of the genomic DNA in both the transformed cancerous cell lines and in carcinogen-induced lung cancer was ascertained by analysis of expressions of certain major lung cancer specific tumour suppressor genes. The other objective was to examine if ultra highly diluted homeopathic drug, Condurango 30C, had ability to modulate DNA methylation. Methods: DNA methylation activity, if any, has been ascertained in H460-NSCLC cells in vitro and in BaP-induced lung cancer of rats in vivo, in respect of tumour suppressor genes like p15, p16, p18 and p53 by using PCR-SSCP analyses. The ability of modulation of DNA methylation, if any, by Condurango 30C was also verified against placebo control in a blinded manner. Results: Condurango 30C-treated DNA showed significant decrease in band-intensity of p15 and p53 genes especially in methylated condition, in vitro, at the IC50 dose (2.43µl/100µl). SSCP analysis of p15 and p53 genes in Condurango 30C-treated DNA also supported ability of Condurango 30C to modulate methylation state, in vitro. Inhibition of p15 hypermethylation was observed after post cancer treatment of rat with Condurango 30C. SSCP results gave a better indication of differences in band-position and single strand separation of p15 and p53 in Condurango 30C treated samples. Conclusion: Condurango 30C could trigger epigenetic modification in lung cancer via modulation of DNA hypermethylation but placebos could not.

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