Abstract B42: An integrated view on genetic and epigenetic mechanisms revealed aberrant DNA methylation as an important source for miRNA deregulation in prostate cancer

Background. Prostate cancer (PCa) is the second most prevalent malignancy among males, characterized by high mortality rates. Aberrant DNA methylation in promoters of tumor suppressor genes is an early and frequent event during prostate carcinogenesis. Modern techniques allow a sensitive detection of DNA methylation biomarkers in bodily fluids from cancer patients offering a noninvasive tool for PCa monitoring. Our study aimed at the analysis of DNA methylation in urine sediments from PCa patients for the selection of most informative noninvasive biomarkers. Material and Methods. Real-time methylation-specific polymerase chain reaction was used for the detection of methylated RASSF1, RARB, and GSTP1 genes in catheterized urine specimens from 34 patients with biopsy-proven early or medium stage PCa. Results. At least one gene was methylated in urine sediments from 28 cases with PCa, with a sensitivity of the test reaching 82%. RASSF1 was methylated in 71% (24 of 34), RARB in 44% (15 of 34), and GSTP1 in 3% (1 of 34) of the specimens. High level of methylation (≥50%) in RARB and RASSF1 genes was detected in 40% and 20% of cases, respectively. A significant association was observed between high level of RARB methylation and Gleason score (P=0.01), while methylation of at least one gene occurred more frequently in urine DNA of older patients (P=0.02). Conclusions. Results of our study show a high sensitivity of DNA methylation biomarkers, especially RASSF1 and RARB, for the early and noninvasive detection of PCa.

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A Revolution in Dentistry: Epigenetics

Dental Journal of Advance Studies ◽

10.1055/s-0039-1685128 ◽

2019 ◽

Vol 07 (01) ◽

pp. 001-005

Author(s):

Namita Sepolia ◽

Deepti Jindal ◽

Sandhya Kaushwaha ◽

Varun Jindal ◽

Monika Negi

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Dna Methyltransferase ◽

Cellular Proliferation ◽

Cpg Islands ◽

Odontogenic Tumors ◽

Epigenetic Mechanisms ◽

Epigenetic Changes ◽

Daughter Cells ◽

Aberrant Dna Methylation

AbstractEpigenetics is the study of potentially heritable changes in gene expression that does not involve changes in underlying DNA sequence. Epigenetic mechanisms play a crucial role in cellular proliferation, migration, and differentiation in both normal and neoplastic development. Epigenetic changes may be inherited and can occur during embryonal development or after birth. Once the change in DNA methylation takes place, following cell division the altered pattern is transferred into daughter cells by the action DNA methyltransferase enzyme, which recognizes hemi-methylated sites and methylates newly synthesized DNA formed during replication. Recently, it has been suggested that aberrant DNA methylation of cytosine-phosphate-guanine (CpG) islands is a common event in odontogenic tumors. Expression of DNA methyltransferase 1,3A,3B has been noted in various odontogenic tumors. Thus, this review aims to study the various epigenetic pathways that are altered in odontogenic tumors.

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The emerging roles of DNA methylation in the clinical management of prostate cancer

Endocrine Related Cancer ◽

10.1677/erc.1.01184 ◽

2006 ◽

Vol 13 (2) ◽

pp. 357-377 ◽

Cited By ~ 51

Author(s):

Antoinette S Perry ◽

Ruth Foley ◽

Karen Woodson ◽

Mark Lawler

Keyword(s):

Prostate Cancer ◽

Dna Methylation ◽

Clinical Management ◽

Epigenetic Modification ◽

Retinoic Acid Receptor ◽

Promoter Hypermethylation ◽

Androgen Independence ◽

Retinoic Acid Receptor Β2 ◽

Key Issues ◽

Aberrant Dna Methylation

Aberrant DNA methylation is one of the hallmarks of carcinogenesis and has been recognized in cancer cells for more than 20 years. The role of DNA methylation in malignant transformation of the prostate has been intensely studied, from its contribution to the early stages of tumour development to the advanced stages of androgen independence. The most significant advances have involved the discovery of numerous targets such as GSTP1, Ras-association domain family 1A (RASSF1A) and retinoic acid receptor β2 (RARβ2) that become inactivated through promoter hypermethylation during the course of disease initiation and progression. This has provided the basis for translational research into methylation biomarkers for early detection and prognosis of prostate cancer. Investigations into the causes of these methylation events have yielded little definitive data. Aberrant hypomethylation and how it impacts upon prostate cancer has been less well studied. Herein we discuss the major developments in the fields of prostate cancer and DNA methylation, and how this epigenetic modification can be harnessed to address some of the key issues impeding the successful clinical management of prostate cancer.

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DNA methylation reprogramming during oogenesis and interference by reproductive technologies: Studies in mouse and bovine models

Reproduction Fertility and Development ◽

10.1071/rd14333 ◽

2015 ◽

Vol 27 (5) ◽

pp. 739 ◽

Cited By ~ 17

Author(s):

Ellen Anckaert ◽

Trudee Fair

Keyword(s):

Dna Methylation ◽

Reproductive Technologies ◽

Reproductive Technology ◽

Epigenetic Mechanisms ◽

Healthy Development ◽

Early Embryos ◽

Fertility Problems ◽

Aberrant Dna Methylation ◽

Methylation Patterns ◽

The Impact

The use of assisted reproductive technology (ART) to overcome fertility problems has continued to increase since the birth of the first baby conceived by ART over 30 years ago. Similarly, embryo transfer is widely used as a mechanism to advance genetic gain in livestock. Despite repeated optimisation of ART treatments, pre- and postnatal outcomes remain compromised. Epigenetic mechanisms play a fundamental role in successful gametogenesis and development. The best studied of these is DNA methylation; the appropriate establishment of DNA methylation patterns in gametes and early embryos is essential for healthy development. Superovulation studies in the mouse indicate that specific ARTs are associated with normal imprinting establishment in oocytes, but abnormal imprinting maintenance in embryos. A similar limited impact of ART on oocytes has been reported in cattle, whereas the majority of embryo-focused studies have used cloned embryos, which do exhibit aberrant DNA methylation. The present review discusses the impact of ART on oocyte and embryo DNA methylation with regard to data available from mouse and bovine models.

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Absolute Quantitation of DNA Methylation of 28 Candidate Genes in Prostate Cancer Using Pyrosequencing

Disease Markers ◽

10.1155/2011/157829 ◽

2011 ◽

Vol 30 (4) ◽

pp. 151-161 ◽

Cited By ~ 61

Author(s):

Nataڑa Vasiljeviš ◽

Keqiang Wu ◽

Adam R. Brentnall ◽

Dae Cheol Kim ◽

Mangesh A. Thorat ◽

...

Keyword(s):

Prostate Cancer ◽

Dna Methylation ◽

Candidate Genes ◽

Gleason Score ◽

Gene Methylation ◽

Absolute Quantitation ◽

Prostate Hyperplasia ◽

Diagnostic Potential ◽

Aberrant Dna Methylation ◽

Benign Prostate

Aberrant DNA methylation plays a pivotal role in carcinogenesis and its mapping is likely to provide biomarkers for improved diagnostic and risk assessment in prostate cancer (PCa). We quantified and compared absolute methylation levels among 28 candidate genes in 48 PCa and 29 benign prostate hyperplasia (BPH) samples using the pyrosequencing (PSQ) method to identify genes with diagnostic and prognostic potential.RARB, HIN1, BCL2, GSTP1, CCND2, EGFR5, APC, RASSF1A, MDR1, NKX2-5, CDH13, DPYS, PTGS2, EDNRB, MAL, PDLIM4, HLAa, ESR1andTIG1were highly methylated in PCa compared to BPH (p < 0.001), whileSERPINB5, CDH1, TWIST1, DAPK1, THRB, MCAM, SLIT2, CDKN2aandSFNwere not. RARB methylation above 21% completely distinguished PCa from BPH. Separation based on methylation level ofSFN, SLIT2andSERPINB5distinguished low and high Gleason score cancers, e.g.SFNandSERPINB5together correctly classified 81% and 77% of high and low Gleason score cancers respectively. Several genes includingCDH1previously reported as methylation markers in PCa were not confirmed in our study. Increasing age was positively associated with gene methylation (p < 0.0001).Accurate quantitative measurement of gene methylation in PCa appears promising and further validation of genes likeRARB, HIN1, BCL2, APC and GSTP1is warranted for diagnostic potential andSFN, SLIT2andSERPINB5for prognostic potential.

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