A5036633061- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Acute Myeloid Leukemia Research
- Cancer Genomics and Diagnostics
- Cancer-related gene regulation
- Gut microbiota and health
- Otolaryngology and Infectious Diseases
- Diverticular Disease and Complications
- Adipokines, Inflammation, and Metabolic Diseases
- Adipose Tissue and Metabolism
- Histone Deacetylase Inhibitors Research
- Genomics and Chromatin Dynamics
- Cancer-related molecular mechanisms research
- Nutrition, Genetics, and Disease
- Gene expression and cancer classification
- Prostate Cancer Treatment and Research
- Lung Cancer Treatments and Mutations
- Anorectal Disease Treatments and Outcomes
- Chronic Myeloid Leukemia Treatments
- Chromosomal and Genetic Variations
- Diet and metabolism studies
- Bioinformatics and Genomic Networks
- Genomic variations and chromosomal abnormalities
- Enterobacteriaceae and Cronobacter Research
- Ferroptosis and cancer prognosis
The University of Texas MD Anderson Cancer Center
2016-2025
Genesis Foundation
2000-2020
Epigenomics (Germany)
2020
Gunma University
2019
Akita Red Cross Hospital
2014
Fujita Health University
2013-2014
Iwate Medical University
2014
Aichi Cancer Center
2007-2014
Molecular Oncology (United States)
2014
Sapporo Medical University
2014
We report a method for studying global DNA methylation based on using bisulfite treatment of and simultaneous PCR multiple repetitive elements, such as Alu elements long interspersed nucleotide (LINE). The product, which represents pool approximately 15 000 genomic loci, could be used direct sequencing, selective restriction digestion or pyrosequencing, in order to quantitate methylation. By the assay was reproducible with standard deviation only 2% between assays. Using this we found that...
The functional roles of SNPs within the 8q24 gene desert in cancer phenotype are not yet well understood. Here, we report that CCAT2 , a novel long noncoding RNA transcript (lncRNA) encompassing rs6983267 SNP, is highly overexpressed microsatellite-stable colorectal and promotes tumor growth, metastasis, chromosomal instability. We demonstrate MYC miR–17–5p, miR–20a up-regulated by through TCF7L2-mediated transcriptional regulation. further identify physical interaction between TCF7L2...
Abstract Fusobacterium species are part of the gut microbiome in humans. Recent studies have identified overrepresentation colorectal cancer tissues, but it is not yet clear whether this pathogenic or simply an epiphenomenon. In study, we evaluated relationship between status and molecular features cancers through quantitative real-time PCR 149 89 adjacent normal appearing mucosae 72 colonic from cancer-free individuals. Results were correlated with CpG island methylator phenotype (CIMP)...
Small cell lung cancer (SCLC) is an aggressive malignancy composed of distinct transcriptional subtypes, but implementing subtyping in the clinic has remained challenging, particularly due to limited tissue availability. Given known epigenetic regulation critical SCLC programs, we hypothesized that subtype-specific patterns DNA methylation could be detected tumor or blood from patients. Using genomic-wide reduced-representation bisulfite sequencing (RRBS) two cohorts totaling 179 patients...
Abstract 5-Aza-2′-deoxycytidine (decitabine) is postulated to have clinical activity in myeloid leukemias via its ability inhibit DNA methylation. To study this, we examined methylation patients with leukemia treated decitabine. Five days after the treatment, total genomic 5-methylcytosine/cytosine decreased on average by 14% (from 4.3% 3.7%), whereas of repetitive elements showed a mean decrease 9% and 16% for Alu long interspersed nucleotide elements, respectively. Methylation linearly...
BackgroundAlterations in DNA methylation cancer include global hypomethylation and gene-specific hypermethylation. It is not clear whether these two epigenetic errors are mechanistically linked or occur independently. This study was performed to determine the relationship between hypomethylation, hypermethylation microsatellite instability cancer.Methodology/Principal FindingsWe examined 61 cell lines 60 colorectal carcinomas their adjacent tissues using LINE-1 bisulfite-PCR as a surrogate...
An abnormal pattern of DNA methylation occurs at specific genes in almost all neoplasms. The lack high-throughput methods with high specificity and sensitivity to detect changes has limited its application for clinical profiling. Here we overcome this limitation present an improved method identify methylated genome-wide by hybridizing a CpG island microarray amplicons obtained the amplification technique (MCAM). We validated three cancer cell lines 15 primary colorectal tumors, resulting...
DNA methylation is a heritable epigenetic mark, enabling stable but reversible gene repression. In mammalian cells, methyltransferases (DNMTs) are responsible for modifying cytosine to 5-methylcytosine (5mC), which can be further oxidized by the TET dioxygenases ultimately cause demethylation. However, genome-wide cooperation and functions of these two families proteins, especially at large under-methylated regions, called canyons, remain largely unknown. Here we demonstrate that DNMT3A TET1...
DNMT3L (DNMT3-like), a member of the DNMT3 family, has no DNA methyltransferase activity but regulates de novo methylation. While biochemical studies show that is capable interacting with both DNMT3A and DNMT3B stimulating their enzymatic activities, genetic evidence suggests essential for DNMT3A-mediated methylation in germ cells dispensable during embryogenesis, which mainly mediated by DNMT3B. How what determines its functional specificity are not well understood. Here we DNMT3L-deficient...
DNA methylation is commonly thought of as a "molecular lock" that leads to permanent gene silencing. To investigate this notion, we tested 24 different histone deacetylase inhibitors (HDACi) on colon cancer cells harbor GFP locus stably integrated and silenced by hypermethylated cytomegalovirus (CMV) promoter. We found HDACi efficiently reactivated expression many other endogenous genes hypermethylation. After treatment, all promoters were marked with active chromatin, yet hypermethylation...
Current treatment regimens for pancreatic ductal adenocarcinoma (PDAC) yield poor 5-year survival, emphasizing the critical need to identify druggable targets essential PDAC maintenance. We developed an unbiased and in vivo target discovery approach molecular vulnerabilities low-passage patient-derived xenografts or genetically engineered mouse model-derived allografts. Focusing on epigenetic regulators, we identified WDR5, a core member of COMPASS histone H3 Lys4 (H3K4) MLL (1-4)...
Ductal carcinoma in situ (DCIS) is a noninvasive precursor lesion to invasive breast carcinoma. We still have no understanding on why only some DCIS lesions evolve cancer whereas others appear not do so during the life span of patient. Here, we performed full exome (tumor vs. matching normal), transcriptome, and methylome analysis 30 pure high-grade (HG-DCIS) 10 normal epithelial samples. Sixty-two percent HG-DCIS cases displayed mutations affecting driver genes or potential drivers....
TET1 is a 5-methylcytosine dioxygenase and its DNA demethylating activity has been implicated in pluripotency reprogramming. However, the precise role of methylation regulation outside developmental reprogramming still unclear. Here, we show that overexpression catalytic domain but not full length (TET1-FL) induces massive global demethylation differentiated cells. Genome-wide mapping reveals 5-hydroxymethylcytosine production by TET1-FL inhibited as increases, which can be explained...
TET2 enzymatically converts 5-methyl-cytosine to 5-hydroxymethyl-cytosine, possibly leading loss of DNA methylation. mutations are common in myeloid leukemia and were proposed contribute leukemogenesis through To expand on this concept, we studied chronic myelomonocytic (CMML) samples. missense or nonsense detected 53% (16/30) patients. In contrast, only 1/30 patient had a mutation IDH1 IDH2, none them DNMT3A the sites most frequently mutated leukemia. Using bisulfite pyrosequencing, global...
Abstract The mechanism by which anti-cancer immunity shapes early carcinogenesis of lung adenocarcinoma (ADC) is unknown. In this study, we characterize the immune contexture invasive ADC and its precursors transcriptomic profiling, T cell receptor (TCR) sequencing multiplex immunofluorescence (mIF). Our results demonstrate that anti-tumor evolved as a continuum from preneoplasia, to preinvasive ADC, minimally-invasive frankly with gradually less effective more intensively regulated response...
Abstract The evolution of DNA methylome and methylation intra-tumor heterogeneity (ITH) during early carcinogenesis lung adenocarcinoma has not been systematically studied. We perform reduced representation bisulfite sequencing invasive its precursors, atypical adenomatous hyperplasia, in situ minimally adenocarcinoma. observe gradual increase aberrations significantly higher level ITH later-stage lesions. phylogenetic patterns inferred from resemble those based on somatic mutations...
Maintenance of genomic methylation patterns at DNA replication forks by DNMT1 is the key to faithful mitotic inheritance. often overexpressed in cancer cells and hypomethylating agents azacytidine decitabine are currently used treatment hematologic malignancies. However, toxicity these cytidine analogs their ineffectiveness treating solid tumors have limited wider clinical use. GSK-3484862 a newly-developed, dicyanopyridine containing, non-nucleoside DNMT1-selective inhibitor with low...
The epigenetic impact of DNA methylation in chronic myelogenous leukemia (CML) is not completely understood. To elucidate its role we analyzed 120 patients with CML for promoter-associated CpG islands 10 genes. Five genes were identified by screening the K562 cell line and 3 myeloproliferative neoplasms. CDKN2B gene was selected frequent myeloid malignancies ABL1 as target BCR-ABL translocation. Thirty imatinib-naïve (mostly treated interferon-alpha before imatinib era), 30...
A better understanding of key molecular changes during the pathogenesis melanoma could impact strategies to reduce mortality from this cancer. Two epigenetic events involved in cancer are hypermethylation tumor-suppressor gene promoters associated with transcriptional repression and hypomethylation reexpression genomic instability. We analyzed 16 cell lines for aberrant 15 cancer-linked genes (ERα, MGMT, RARβ2, RIL, RASSF1A, PAX7, PGRβ, PAX2, NKX2-3, OLIG2, HAND1, ECAD, CDH13, MLH1, p16) two...