The detection of DNA methylation of tumour suppressor genes in cervical high‐grade squamous intraepithelial lesion: A prospective cytological‐histological correlation study of 70 cases

Cytopathology ◽  
2019 ◽  
Vol 30 (4) ◽  
pp. 426-431
Author(s):  
Ondrej Ondič ◽  
Jana Němcová ◽  
Reza Alaghehbandan ◽  
Kateřina Černá ◽  
Barbora Gomolčáková ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Correlation Study ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
High Grade ◽  
Squamous Intraepithelial Lesion ◽  
Suppressor Genes ◽  
Intraepithelial Lesion

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 Biomarker Expression in Multifocal Vulvar High-Grade Squamous Intraepithelial Lesions

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5646
Author(s):  
Nikki B. Thuijs ◽  
Willemijn A. M. Schonck ◽  
Linde L. J. Klaver ◽  
Guus Fons ◽  
Marc van Beurden ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Expression Profiles ◽  
High Grade ◽  
Squamous Intraepithelial Lesion ◽  
Predictive Diagnostics ◽  
Ki 67 ◽  
Intraepithelial Lesion ◽  
Prospective Longitudinal ◽  
Intraepithelial Lesions ◽  
Six Genes

In patients with high-grade squamous intraepithelial lesion (HSIL) of the vulva, the presence of multiple lesions, called multifocal HSIL, is common. The aim of this exploratory study was to investigate biomarker expression profiles in multifocal HSIL. In total, 27 lesions from 12 patients with high-risk human papillomavirus (HPV)-positive multifocal HSIL were tested for HPV genotype, expression of p16INK4a and Ki-67, and DNA methylation of six genes. HPV16 was found most commonly in 21 (77.8%) HSILs. In two (16.4%) patients, HPV genotype differed between the lesions. All lesions demonstrated diffuse p16INK4a staining, of which three (11.1%) were combined with patchy staining. One patient (8.3%) demonstrated markedly different DNA methylation levels between lesions. Generally, heterogeneity in methylation profiles was observed between different patients, even when other biomarkers showed similar expression. In conclusion, this study is the first to demonstrate heterogeneity of individual lesions in patients with multifocal HSIL. The studied biomarkers have the potential to refine prognostic and predictive diagnostics. Future prospective, longitudinal studies are needed to further explore the potential of a biomarker profile for management of patients with multifocal HSIL.

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 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.

scholarly journals SFRP Tumour Suppressor Genes Are Potential Plasma-Based Epigenetic Biomarkers for Malignant Pleural Mesothelioma

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Yuen Yee Cheng ◽  
Ellie Mok ◽  
Sarah Tan ◽  
Catherine Leygo ◽  
Chris McLaughlin ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Chronic Inflammation ◽  
Malignant Pleural Mesothelioma ◽  
Asbestos Exposure ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Pleural Mesothelioma ◽  
Gene Promoters ◽  
Suppressor Genes ◽  
Epigenetic Biomarkers

Malignant pleural mesothelioma (MPM) is associated with asbestos exposure. Asbestos can induce chronic inflammation which in turn can lead to silencing of tumour suppressor genes. Wnt signaling pathway can be affected by chronic inflammation and is aberrantly activated in many cancers including colon and MPM. SFRP genes are antagonists of Wnt pathway, and SFRPs are potential tumour suppressors in colon, gastric, breast, ovarian, and lung cancers and mesothelioma. This study investigated the expression and DNA methylation of SFRP genes in MPM cells lines with and without demethylation treatment. Sixty-six patient FFPE samples were analysed and have showed methylation of SFRP2 (56%) and SFRP5 (70%) in MPM. SFRP2 and SFRP5 tumour-suppressive activity in eleven MPM lines was confirmed, and long-term asbestos exposure led to reduced expression of the SFRP1 and SFRP2 genes in the mesothelium (MeT-5A) via epigenetic alterations. Finally, DNA methylation of SFRPs is detectable in MPM patient plasma samples, with methylated SFRP2 and SFRP5 showing a tendency towards greater abundance in patients. These data suggested that SFRP genes have tumour-suppresive activity in MPM and that methylated DNA from SFRP gene promoters has the potential to serve as a biomarker for MPM patient plasma.

scholarly journals Epigenetic inactivation of tumour suppressor coding and non-coding genes in human cancer: an update

Open Biology ◽  
2017 ◽  
Vol 7 (9) ◽  
pp. 170152 ◽  
Author(s):  
Pere Llinàs-Arias ◽  
Manel Esteller
Keyword(s):  
Dna Methylation ◽  
Human Cancer ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Molecular Pathways ◽  
Metabolic Shift ◽  
Therapeutic Approaches ◽  
Suppressor Genes ◽  
Epigenetic Inactivation ◽  
Epigenetic Events

Cancer cells undergo many different alterations during their transformation, including genetic and epigenetic events. The controlled division of healthy cells can be impaired through the downregulation of tumour suppressor genes. Here, we provide an update of the mechanisms in which epigenetically altered coding and non-coding tumour suppressor genes are implicated. We will highlight the importance of epigenetics in the different molecular pathways that lead to enhanced and unlimited capacity of division, genomic instability, metabolic shift, acquisition of mesenchymal features that lead to metastasis, and tumour plasticity. We will briefly describe these pathways, focusing especially on genes whose epigenetic inactivation through DNA methylation has been recently described, as well as on those that are well established as being epigenetically silenced in cancer. A brief perspective of current clinical therapeutic approaches that can revert epigenetic inactivation of non-coding tumour suppressor genes will also be given.

Clofarabine, a novel adenosine analogue, reactivates DNA methylation-silenced tumour suppressor genes and inhibits cell growth in breast cancer cells

2014 ◽  
Vol 723 ◽  
pp. 276-287 ◽  
Author(s):  
Katarzyna Lubecka-Pietruszewska ◽  
Agnieszka Kaufman-Szymczyk ◽  
Barbara Stefanska ◽  
Barbara Cebula-Obrzut ◽  
Piotr Smolewski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Cell Growth ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
Suppressor Genes ◽  
Adenosine Analogue

Specific Genomic Alterations in High-Grade Pulmonary Neuroendocrine Tumours with Carcinoid Morphology

2020 ◽  
Vol 111 (1-2) ◽  
pp. 158-169 ◽  
Author(s):  
Jerôme Cros ◽  
Nathalie Théou-Anton ◽  
Valérie Gounant ◽  
Remy Nicolle ◽  
Cécile Reyes ◽  
...  
Keyword(s):  
Neuroendocrine Tumours ◽  
Genetic Alterations ◽  
Copy Number Variations ◽  
Chromatin Remodelling ◽  
Tumour Suppressor ◽  
Tumour Suppressor Genes ◽  
High Grade ◽  
Ki 67 ◽  
Suppressor Genes ◽  
Genetic Landscape

<b><i>Introduction:</i></b> High-grade lung neuroendocrine tumours with carcinoid morphology have been recently reported; they may represent the thoracic counterparts of grade 3 digestive neuroendocrine tumours. We aimed to study their genetic landscape including analysis of tumoral heterogeneity. <b><i>Methods:</i></b> Eleven patients with high-grade (&#x3e;20% Ki-67 and/or &#x3e;10 mitoses) lung neuroendocrine tumours with a carcinoid morphology were included. We analysed copy number variations, somatic mutations, and protein expression in 16 tumour samples (2 samples were available for 5 patients allowing us to study spatial and temporal heterogeneity). <b><i>Results:</i></b> Genomic patterns were heterogeneous ranging from “quiet” to tetraploid, heavily rearranged genomes. Oncogene mutations were rare and most genetic alterations targeted tumour suppressor genes. Chromosomes 11 (7/11), 3 (6/11), 13 (4/11), and 6–17 (3/11) were the most frequently lost. Altered tumour suppressor genes were common to both carcinoids and neuroendocrine carcinomas, involving different pathways including chromatin remodelling (<i>KMT2A</i>, <i>ARID1A</i>, <i>SETD2</i>, <i>SMARCA2</i>, <i>BAP1</i>, <i>PBRM1</i>, <i>KAT6A</i>), DNA repair (<i>MEN1</i>, <i>POLQ</i>, <i>ATR</i>, <i>MLH1</i>, <i>ATM</i>), cell cycle (<i>RB1</i>, <i>TP53</i>, <i>CDKN2A</i>), cell adhesion (<i>LATS2</i>, <i>CTNNB1</i>, <i>GSK3B</i>) and metabolism (<i>VHL</i>). Comparative spatial/temporal analyses confirmed that these tumours emerged from clones of lower aggressivity but revealed that they were genetically heterogeneous accumulating “neuroendocrine carcinoma-like” genetic alterations through progression such as <i>TP53/RB1</i> alterations. <b><i>Conclusion:</i></b> These data confirm the importance of chromatin remodelling genes in pulmonary carcinoids and highlight the potential role of <i>TP53</i> and <i>RB1</i> to drive the transformation in more aggressive high-grade tumours.

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