scholarly journals Recurrent patterns of DNA methylation in theZNF154,CASP8, andVHLpromoters across a wide spectrum of human solid epithelial tumors and cancer cell lines

Epigenetics ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. 1355-1372 ◽  
Author(s):  
Francisco Sánchez-Vega ◽  
Valer Gotea ◽  
Hanna M Petrykowska ◽  
Gennady Margolin ◽  
Thomas C Krivak ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Wide Spectrum ◽  
Cancer Cell Lines ◽  
Epithelial Tumors ◽  
Recurrent Patterns

scholarly journals Association of expression of epigenetic molecular factors with DNA methylation and sensitivity to chemotherapeutic agents in cancer cell lines

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Suleyman Vural ◽  
Alida Palmisano ◽  
William C. Reinhold ◽  
Yves Pommier ◽  
Beverly A. Teicher ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Antitumor Agents ◽  
Cancer Cell Lines ◽  
Chemotherapeutic Agents ◽  
Epigenetic Factors ◽  
Expression Of Genes ◽  
Genes Encoding

Abstract Background Altered DNA methylation patterns play important roles in cancer development and progression. We examined whether expression levels of genes directly or indirectly involved in DNA methylation and demethylation may be associated with response of cancer cell lines to chemotherapy treatment with a variety of antitumor agents. Results We analyzed 72 genes encoding epigenetic factors directly or indirectly involved in DNA methylation and demethylation processes. We examined association of their pretreatment expression levels with methylation beta-values of individual DNA methylation probes, DNA methylation averaged within gene regions, and average epigenome-wide methylation levels. We analyzed data from 645 cancer cell lines and 23 cancer types from the Cancer Cell Line Encyclopedia and Genomics of Drug Sensitivity in Cancer datasets. We observed numerous correlations between expression of genes encoding epigenetic factors and response to chemotherapeutic agents. Expression of genes encoding a variety of epigenetic factors, including KDM2B, DNMT1, EHMT2, SETDB1, EZH2, APOBEC3G, and other genes, was correlated with response to multiple agents. DNA methylation of numerous target probes and gene regions was associated with expression of multiple genes encoding epigenetic factors, underscoring complex regulation of epigenome methylation by multiple intersecting molecular pathways. The genes whose expression was associated with methylation of multiple epigenome targets encode DNA methyltransferases, TET DNA methylcytosine dioxygenases, the methylated DNA-binding protein ZBTB38, KDM2B, SETDB1, and other molecular factors which are involved in diverse epigenetic processes affecting DNA methylation. While baseline DNA methylation of numerous epigenome targets was correlated with cell line response to antitumor agents, the complex relationships between the overlapping effects of each epigenetic factor on methylation of specific targets and the importance of such influences in tumor response to individual agents require further investigation. Conclusions Expression of multiple genes encoding epigenetic factors is associated with drug response and with DNA methylation of numerous epigenome targets that may affect response to therapeutic agents. Our findings suggest complex and interconnected pathways regulating DNA methylation in the epigenome, which may both directly and indirectly affect response to chemotherapy.

scholarly journals Hemimethylation Patterns in Breast Cancer Cell Lines

2019 ◽  
Vol 18 ◽  
pp. 117693511987295 ◽  
Author(s):  
Shuying Sun ◽  
Yu Ri Lee ◽  
Brittany Enfield
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Tumor Growth ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Entire Genome ◽  
Cpg Sites

DNA methylation is an epigenetic event that involves adding a methyl group to the cytosine (C) site, especially the one that pairs with a guanine (G) site (ie, CG or CpG site), in a human genome. This event plays an important role in both cancerous and normal cell development. Previous studies often assume symmetric methylation on both DNA strands. However, asymmetric methylation, or hemimethylation (methylation that occurs only on 1 DNA strand), does exist and has been reported in several studies. Due to the limitation of previous DNA methylation sequencing technologies, researchers could only study hemimethylation on specific genes, but the overall genomic hemimethylation landscape remains relatively unexplored. With the development of advanced next-generation sequencing techniques, it is now possible to measure methylation levels on both forward and reverse strands at all CpG sites in an entire genome. Analyzing hemimethylation patterns may potentially reveal regions related to undergoing tumor growth. For our research, we first identify hemimethylated CpG sites in breast cancer cell lines using Wilcoxon signed rank tests. We then identify hemimethylation patterns by grouping consecutive hemimethylated CpG sites based on their methylation states, methylation “M” or unmethylation “U.” These patterns include regular (or consecutive) hemimethylation clusters (eg, “MMM” on one strand and “UUU” on another strand) and polarity (or reverse) clusters (eg, “MU” on one strand and “UM” on another strand). Our results reveal that most hemimethylation clusters are the polarity type, and hemimethylation does occur across the entire genome with notably higher numbers in the breast cancer cell lines. The lengths or sizes of most hemimethylation clusters are very short, often less than 50 base pairs. After mapping hemimethylation clusters and sites to corresponding genes, we study the functions of these genes and find that several of the highly hemimethylated genes may influence tumor growth or suppression. These genes may also indicate a progressing transition to a new tumor stage.

High concordance between DNA methylation of tumor suppressor loci in pancreatic cancer cell lines and their corresponding primary carcinoma

2000 ◽  
Vol 118 (4) ◽  
pp. A46
Author(s):  
Takashi Ueki ◽  
Minoru Toyota ◽  
Kimberly M. Walter ◽  
Elizabeth Jaffee ◽  
Charles J. Yeo ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Dna Methylation ◽  
Tumor Suppressor ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Primary Carcinoma ◽  
High Concordance

Translational disequilibrium as an interference marker to study miRNA and methylation silencing of APRIN, a stem cell regulator in breast cancer microchimerism

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11109-11109
Author(s):  
P. Geck ◽  
V. Denes ◽  
M. Pilichowska ◽  
A. Makarovskiy ◽  
G. A. Carpinito
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Stem Cell ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Fetal Microchimerism ◽  
Clinical Breast

11109 Background: Gene silencing is universally observed in cancer and involves promoter DNA methylation. We found that a cohesin-related stem cell regulator, APRIN (Pds5B) was silenced in breast cancer clinical samples. Surprisingly, in 40% of these samples DNA methylation was not involved. Furthermore, in some breast cancer cell lines the APRIN protein was silenced without transcript downregulation or promoter methylation. This “translational disequilibrium” has been frequently reported with other proteins, but without mechanistic explanations. Recent results with RNA interference indicate that gene repression through microRNAs (typically mismatched) is mostly translational without transcript degradation. We propose, therefore, that the puzzling translational disequilibrium phenomenon is a new form of epigenetic silencing by miRNA mechanisms. We aim (i) to verify miRNA epigenetics of APRIN silencing in breast cancer cell lines; (ii) to study clinical breast cancer samples for methylation vs. miRNAs mechanisms in APRIN translational disequilibrium; and (iii) to investigate if miRNA silencing of APRIN affects a fetal embryonic stem cell pool in breast cancer (microchimerism). Methods: (i) We used miRNA mimics and miRNA inhibitors in breast cancer cell lines to verify specific miRNA involvement in APRIN silencing. (ii) We used immunohistochemistry with bisulfite converted DNA for methylation and microdissected RNA for microRNA interference studies from 56 clinical breast cancer samples. (iii) We used Y-chromosome markers on microdissected DNA for fetal microchimerism studies. Results: (i) We found that in breast cancer cell lines with APRIN translational disequilibrium a set of microRNAs correlate with APRIN silencing. (ii) We found miRNA related mechanisms in about 35 percent of breast cancer samples where APRIN was silenced and (iii) APRIN may specifically affect stem cells of fetal origin in the mother's mammary gland and contribute to cancer. Conclusions: The novel miRNA-based mechanism maybe a new epigenetic factor of gene silencing in cancer. We experimentally confirmed a set of APRIN specific miRNAs and established preliminary correlations with fetal microchimerism in breast cancer. No significant financial relationships to disclose.

DNA Methylation Profiles of Organic Anion Transporting Polypeptide 1B3 in Cancer Cell Lines

2010 ◽  
Vol 27 (3) ◽  
pp. 510-516 ◽  
Author(s):  
Sayaka Ichihara ◽  
Ryota Kikuchi ◽  
Hiroyuki Kusuhara ◽  
Satoki Imai ◽  
Kazuya Maeda ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cell Lines ◽  
Cancer Cell ◽  
Organic Anion ◽  
Cancer Cell Lines ◽  
Organic Anion Transporting Polypeptide

A novel DNA methylation marker for the urine-based liquid biopsies to detect bladder cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16503-e16503
Author(s):  
Tao Zeng ◽  
Huanhuan Deng ◽  
Rongsong Zhao ◽  
Longwu Huang ◽  
Yun Gong ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bladder Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Cancer Cell Lines ◽  
Urine Samples ◽  
Bladder Cancer Cell ◽  
Epithelial Cell Line ◽  
Methylation Marker ◽  
Normal Bladder

e16503 Background: For bladder cancer (BC), the 5-year survival rate for patients with localized tumors can reach as high as 92%, but only 45% for those with tumors spreading to nearby regions. Cystoscopy combined with tissue biopsy can miss 10-40% of the cancer cases due to multiple factors. Meanwhile, the method is invasive, causing physical discomfort and psychological trauma for the patients. Therefore, development of a noninvasive, sensitive, and specific diagnostic alternative is needed. By analyzing TCGA data and improving analytic technology currently available, we have developed an easy-to-use, convenient, and accurate detection approach for BC relying on a single methylation marker. Methods: We searched TCGA database and selected a total of 366 candidate markers including those that have been published for subsequent examination and analyzed 446 primer pairs and probe sets. Using quantitative methylight method, we narrowed the field down to top 5 performers for subsequent urine-based testing of 270 samples. Finally, two markers were selected for validation testing in a group of 530 urine samples, consisting of 161 bladder cancers, 244 normal controls, 80 renal carcinomas, and 45 carcinomas of renal pelvis and ureter. In addition, we detected the methylation level and mRNA expression of target gene in 8 bladder cancer cell lines and 1 normal bladder epithelial cell line by MSP, qMSP and qPCR. Results: Methylation marker DMRTA2 had a sensitivity of 85.7%, an AUC value of 0.924, and an accuracy of 90.6%. The specificity, from a control group consisting of patients with lithangiuria, prostatoplasia, and prostatitis as well as healthy individuals, is 93.9% (138/161). Notably, the methylation assay had the highest sensitivities for tumors at stages of T1 (94.4%) and T2 (96.6%) compared with T3 (80.0%), T4 (71.4%), and unknown stage (90.0%). While methylation was observed in 34/45 urine samples from patients with carcinomas of renal pelvis and ureter, a good sensitivity of 75.6%, it was detected at extremely low rate of 7.5% (6/80) in those with interfering cancers of kidney and prostate. Additionally, the assay specificity was significantly affected by the age of the cancer patients and selection of healthy controls, critical aspects to be carefully considered during the design and development phase of the methylation-specific testing. Compared with SV-HUC-1, the normal bladder epithelial cell line, DMRTA2 gene was hypermethylated in 8 bladder cancer cell lines, which is consistent with the results of MSP and qMSP. The mRNA levels of DMRTA2 were low in some bladder cancer cell lines, such as T24, J82, UM-UC-3 and RT4, however were fairly high levels in 5637, SCaBER, TCCSUP and SW780. Conclusions: Our data demonstrated that a single-target DNA methylation signature could be highly effective to detect bladder cancer via urine samples.

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