scholarly journals Aberrant DNA Methylation and Prostate Cancer

2011 ◽  
Vol 12 (7) ◽  
pp. 486-505 ◽  
Author(s):  
Sunipa Majumdar ◽  
Eric Buckles ◽  
John Estrada ◽  
Shahriar Koochekpour
2010 ◽  
Author(s):  
Masatoshi Watanabe ◽  
Yoshifumi Hirokawa ◽  
Hiroyoshi Suzuki ◽  
Tomohiko Ichikawa ◽  
Takahiko Katoh ◽  
...  

Medicina ◽  
2011 ◽  
Vol 47 (3) ◽  
pp. 20
Author(s):  
Kristina Daniūnaitė ◽  
Artūras Berezniakovas ◽  
Feliksas Jankevičius ◽  
Arvydas Laurinavičius ◽  
Juozas Lazutka ◽  
...  

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.


2006 ◽  
Vol 13 (2) ◽  
pp. 357-377 ◽  
Author(s):  
Antoinette S Perry ◽  
Ruth Foley ◽  
Karen Woodson ◽  
Mark Lawler

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.


2011 ◽  
Vol 30 (4) ◽  
pp. 151-161 ◽  
Author(s):  
Nataڑa Vasiljeviš ◽  
Keqiang Wu ◽  
Adam R. Brentnall ◽  
Dae Cheol Kim ◽  
Mangesh A. Thorat ◽  
...  

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.


2019 ◽  
Author(s):  
Christine Dinh ◽  
Juan Young ◽  
Olena Bracho ◽  
Rahul Mittal ◽  
Denise Yan ◽  
...  

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 245-LB
Author(s):  
MOHAMED M. ALI ◽  
CHANDRA HASSAN ◽  
MARIO MASRUR ◽  
FRANCESCO BIANCO ◽  
SHANE A. PHILLIPS ◽  
...  

Author(s):  
Irfete S. Fetahu ◽  
Sabine Taschner-Mandl

AbstractNeuroblastoma (NB) is a pediatric cancer of the sympathetic nervous system and one of the most common solid tumors in infancy. Amplification of MYCN, copy number alterations, numerical and segmental chromosomal aberrations, mutations, and rearrangements on a handful of genes, such as ALK, ATRX, TP53, RAS/MAPK pathway genes, and TERT, are attributed as underlying causes that give rise to NB. However, the heterogeneous nature of the disease—along with the relative paucity of recurrent somatic mutations—reinforces the need to understand the interplay of genetic factors and epigenetic alterations in the context of NB. Epigenetic mechanisms tightly control gene expression, embryogenesis, imprinting, chromosomal stability, and tumorigenesis, thereby playing a pivotal role in physio- and pathological settings. The main epigenetic alterations include aberrant DNA methylation, disrupted patterns of posttranslational histone modifications, alterations in chromatin composition and/or architecture, and aberrant expression of non-coding RNAs. DNA methylation and demethylation are mediated by DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) proteins, respectively, while histone modifications are coordinated by histone acetyltransferases and deacetylases (HATs, HDACs), and histone methyltransferases and demethylases (HMTs, HDMs). This article focuses predominately on the crosstalk between the epigenome and NB, and the implications it has on disease diagnosis and treatment.


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