dna modification methylases

Summary

Summary: Enzymes that are part of the restriction-modification systems. They are responsible for producing a species-characteristic methylation pattern, on either adenine or cytosine residues, in a specific short base sequence in the host cell's own DNA. This methylated sequence will occur many times in the host-cell DNA and remain intact for the lifetime of the cell. Any DNA from another species which gains entry into a living cell and lacks the characteristic methylation pattern will be recognized by the restriction endonucleases of similar specificity and destroyed by cleavage. Most have been studied in bacterial systems, but a few have been found in eukaryotic organisms.

Top Publications

  1. pmc REBASE--a database for DNA restriction and modification: enzymes, genes and genomes
    Richard J Roberts
    New England Biolabs, Inc, 240 County Road, Ipswich, MA 01938, USA
    Nucleic Acids Res 38:D234-6. 2010
  2. pmc Characterization of DNA methyltransferase specificities using single-molecule, real-time DNA sequencing
    Tyson A Clark
    Pacific Biosciences, 1380 Willow Road, Menlo Park, CA 94025, USA
    Nucleic Acids Res 40:e29. 2012
  3. ncbi Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: a prospective translational study of the German Glioma Network
    Michael Weller
    Department of Neurology, University Hospital Zurich, Zurich, Switzerland
    J Clin Oncol 27:5743-50. 2009
  4. pmc Roles of DNA adenine methylation in host-pathogen interactions: mismatch repair, transcriptional regulation, and more
    Martin G Marinus
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts, Worcester, USA
    FEMS Microbiol Rev 33:488-503. 2009
  5. ncbi Role for DNA methylation in genomic imprinting
    E Li
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142
    Nature 366:362-5. 1993
  6. pmc Prognostic value of three different methods of MGMT promoter methylation analysis in a prospective trial on newly diagnosed glioblastoma
    Arne Christians
    Clinical Cooperation Unit Neuropathology, German Cancer Research Center, DKFZ, Heidelberg, Germany
    PLoS ONE 7:e33449. 2012
  7. ncbi MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients
    Alba A Brandes
    Department of Medical Oncology, Bellaria Maggiore Hospital, Azienda Unità Sanitaria Locale of Bologna, Bologna, Italy
    J Clin Oncol 26:2192-7. 2008
  8. ncbi Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas
    Marc Sanson
    L Institut National de la Santé et de la Recherche Médicale U711, Fédération de Neurologie Mazarin, Groupe Hospitalier Pitie Salpetriere, 75651, Paris Cedex 13, France
    J Clin Oncol 27:4150-4. 2009
  9. pmc Highly integrated single-base resolution maps of the epigenome in Arabidopsis
    Ryan Lister
    Plant Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell 133:523-36. 2008
  10. ncbi Predictive impact of MGMT promoter methylation in glioblastoma of the elderly
    Guido Reifenberger
    Department of Neuropathology, Heinrich Heine University Dusseldorf, Dusseldorf, Germany
    Int J Cancer 131:1342-50. 2012

Research Grants

  1. Diet and DNA methylation in colon mucosa and adenomas
    Jean Pierre Issa; Fiscal Year: 2007
  2. Neoplasia and Methylated CpG Islands Amplification
    Jean Pierre Issa; Fiscal Year: 2004
  3. DNA Methylation in Colon Cancer Metastasis
    Jean Pierre Issa; Fiscal Year: 2008
  4. METHYLATION PROFILING IN COLORECTAL CANCER
    Jean Pierre Issa; Fiscal Year: 2003
  5. A universal DNA endonuclease
    Shuang yong Xu; Fiscal Year: 2005
  6. Cloning and Engineering of Nicking enzymes
    Shuang yong Xu; Fiscal Year: 2004
  7. CANCER AND LEUKEMIA GROUP B--MOUNT SINAI
    Lewis Silverman; Fiscal Year: 2002
  8. Engineering DNA nicking endonucleases
    Shuang yong Xu; Fiscal Year: 2006
  9. A Genetic System Able to Screen for Active DNA Demethylation
    Shuang yong Xu; Fiscal Year: 2006
  10. Genomic & Genetic Characterization of Amplicons in GBMs
    Lynda Chin; Fiscal Year: 2007

Detail Information

Publications263 found, 100 shown here

  1. pmc REBASE--a database for DNA restriction and modification: enzymes, genes and genomes
    Richard J Roberts
    New England Biolabs, Inc, 240 County Road, Ipswich, MA 01938, USA
    Nucleic Acids Res 38:D234-6. 2010
    ..The contents of REBASE may be browsed from the web (http://rebase.neb.com) and selected compilations can be downloaded by ftp (ftp.neb.com). Additionally, monthly updates can be requested via email...
  2. pmc Characterization of DNA methyltransferase specificities using single-molecule, real-time DNA sequencing
    Tyson A Clark
    Pacific Biosciences, 1380 Willow Road, Menlo Park, CA 94025, USA
    Nucleic Acids Res 40:e29. 2012
    ..In addition, we also find evidence of unanticipated MTase promiscuity with some enzymes apparently also modifying sequences that are related, but not identical, to the cognate site...
  3. ncbi Molecular predictors of progression-free and overall survival in patients with newly diagnosed glioblastoma: a prospective translational study of the German Glioma Network
    Michael Weller
    Department of Neurology, University Hospital Zurich, Zurich, Switzerland
    J Clin Oncol 27:5743-50. 2009
    ..The prognostic value of genetic alterations characteristic of glioblastoma in patients treated according to present standards of care is unclear...
  4. pmc Roles of DNA adenine methylation in host-pathogen interactions: mismatch repair, transcriptional regulation, and more
    Martin G Marinus
    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts, Worcester, USA
    FEMS Microbiol Rev 33:488-503. 2009
    ..These roles are diverse and have only partially been understood. Especially intriguing is the evidence that Dam methylation regulates virulence genes in Escherichia coli, Salmonella, and Yersinia at the posttranscriptional level...
  5. ncbi Role for DNA methylation in genomic imprinting
    E Li
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142
    Nature 366:362-5. 1993
    ..Our results demonstrate that a normal level of DNA methylation is required for controlling differential expression of the paternal and maternal alleles of imprinted genes...
  6. pmc Prognostic value of three different methods of MGMT promoter methylation analysis in a prospective trial on newly diagnosed glioblastoma
    Arne Christians
    Clinical Cooperation Unit Neuropathology, German Cancer Research Center, DKFZ, Heidelberg, Germany
    PLoS ONE 7:e33449. 2012
    ....
  7. ncbi MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients
    Alba A Brandes
    Department of Medical Oncology, Bellaria Maggiore Hospital, Azienda Unità Sanitaria Locale of Bologna, Bologna, Italy
    J Clin Oncol 26:2192-7. 2008
    ..The radiologic images obtained in this setting can be difficult to interpret since they may show radiation-induced pseudoprogression (psPD) rather than disease progression...
  8. ncbi Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas
    Marc Sanson
    L Institut National de la Santé et de la Recherche Médicale U711, Fédération de Neurologie Mazarin, Groupe Hospitalier Pitie Salpetriere, 75651, Paris Cedex 13, France
    J Clin Oncol 27:4150-4. 2009
    ..Unexpected mutations affecting the isocitrate dehydrogenase (IDH1) gene at codon 132 have been found in 12% of glioblastomas...
  9. pmc Highly integrated single-base resolution maps of the epigenome in Arabidopsis
    Ryan Lister
    Plant Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Cell 133:523-36. 2008
    ..Finally, strand-specific mRNA-seq revealed altered transcript abundance of hundreds of genes, transposons, and unannotated intergenic transcripts upon modification of the DNA methylation state...
  10. ncbi Predictive impact of MGMT promoter methylation in glioblastoma of the elderly
    Guido Reifenberger
    Department of Neuropathology, Heinrich Heine University Dusseldorf, Dusseldorf, Germany
    Int J Cancer 131:1342-50. 2012
    ..Taken together, MGMT promoter methylation may be a useful biomarker to stratify elderly glioblastoma patients for treatment with versus without alkylating agent CT...
  11. ncbi Prognostic value of O6-methylguanine-DNA methyltransferase status in glioblastoma patients, assessed by five different methods
    Lucie Karayan-Tapon
    Universite de Poitiers, 86021 Poitiers, France
    J Neurooncol 97:311-22. 2010
    ..These results confirm the prognostic value of MGMT promoter methylation in glioblastoma patients initially treated with TMZ. SQ-MSP allowed better discrimination than classical MSP, and pyrosequencing represented a good option...
  12. ncbi Clinical features, mechanisms, and management of pseudoprogression in malignant gliomas
    Dieta Brandsma
    Department of Neuro Oncology, Daniel den Hoed Cancer Centre, Erasmus Medical Centre, Rotterdam, Netherlands
    Lancet Oncol 9:453-61. 2008
    ..Further research is needed to establish reliable imaging parameters that distinguish between true tumour progression and pseudoprogression or treatment-related necrosis...
  13. ncbi Recurrence pattern after temozolomide concomitant with and adjuvant to radiotherapy in newly diagnosed patients with glioblastoma: correlation With MGMT promoter methylation status
    Alba A Brandes
    Department of Medical Oncology, Azienda USL Bellaria Maggiore Hospital, Bologna, Italy
    J Clin Oncol 27:1275-9. 2009
    ....
  14. pmc MGMT promoter methylation, loss of expression and prognosis in 855 colorectal cancers
    Kaori Shima
    Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA
    Cancer Causes Control 22:301-9. 2011
    ..MGMT promoter hypermethylation and epigenetic silencing often occur as early events in carcinogenesis. However, prognostic significance of MGMT alterations in colorectal cancer remains uncertain...
  15. ncbi MGMT promoter hypermethylation and its associations with genetic alterations in a series of 350 brain tumors
    Marta Mellai
    Neuro bio oncology Center, Policlinico di Monza Foundation, Via Pietro Micca, 29 13100, Vercelli, Italy
    J Neurooncol 107:617-31. 2012
    ..In low-grade gliomas, MGMT hypermethylation, but not MGMT protein expression, was associated with a trend, only, toward better survival, in contrast with GBMs, for which it had favorable prognostic significance...
  16. pmc Loss of the mismatch repair protein MSH6 in human glioblastomas is associated with tumor progression during temozolomide treatment
    Daniel P Cahill
    Molecular Pathology Unit, Neurosurgical Service, Brain Tumor Center, and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
    Clin Cancer Res 13:2038-45. 2007
    ..However, the extent of involvement of MSH6 in glioblastoma is unknown. We sought to determine the overall frequency and clinical relevance of MSH6 alterations in glioblastomas...
  17. ncbi A hypermethylated phenotype is a better predictor of survival than MGMT methylation in anaplastic oligodendroglial brain tumors: a report from EORTC study 26951
    Martin J van den Bent
    Neuro Oncology Unit, Department of Neurology, Daniel den Hoed Cancer Center Erasmus Medical Center, Rotterdam, The Netherlands
    Clin Cancer Res 17:7148-55. 2011
    ..Subsequent studies indicated that MGMT promoter methylation is a prognostic marker even in patients treated with radiotherapy alone, both in GBMs and in grade III gliomas...
  18. ncbi A distinct region of the MGMT CpG island critical for transcriptional regulation is preferentially methylated in glioblastoma cells and xenografts
    Deborah S Malley
    Division of Molecular Histopathology, Department of Pathology, Level 3, Lab Block, Addenbrooke s Hospital, University of Cambridge, Cambridge, CB2 0QQ, UK
    Acta Neuropathol 121:651-61. 2011
    ....
  19. ncbi The HaeIV restriction modification system of Haemophilus aegyptius is encoded by a single polypeptide
    A Piekarowicz
    Institute of Microbiology, University of Warsaw, Nowy Swiat 67, Warsaw, 00 046, Poland
    J Mol Biol 293:1055-65. 1999
    ..The MTase activity modified symmetrically located adenine residues on both strands within the recognition sequence yielding N6-methyl adenine. Furthermore, the MTase was active as a dimer...
  20. ncbi MGMT analysis at DNA, RNA and protein levels in glioblastoma tissue
    Matthias Preusser
    Department of Internal Medicine I, Medical University of Vienna, Waehringer Guertel 18 20, Vienna, Austria
    Histol Histopathol 24:511-8. 2009
    ..Further studies may be helpful to establish more appropriate protocols for tumour tissue preservation (e.g. identification of alternative fixatives that do not deteriorate DNA and RNA quality)...
  21. pmc Phasevarions mediate random switching of gene expression in pathogenic Neisseria
    Yogitha N Srikhanta
    School of Molecular and Microbial Sciences, The University of Queensland, St Lucia, Brisbane, Queensland, Australia
    PLoS Pathog 5:e1000400. 2009
    ..This study, in conjunction with our previous work in H. influenzae, indicates that phasevarions may be a common strategy used by host-adapted bacterial pathogens to randomly switch between "differentiated" cell types...
  22. ncbi Evolutionary role of restriction/modification systems as revealed by comparative genome analysis
    E P Rocha
    Atelier de BioInformatique, Universite Paris VI, 75005 Paris, France
    Genome Res 11:946-58. 2001
    ..As a consequence, RMSs constitute a nontrivial third player in the host-parasite relationship between bacteria and phages...
  23. ncbi Correlation between promoter hypermethylation of GSTP1 and response to chemotherapy in diffuse large B cell lymphoma
    Itsuko Nakamichi
    Department of Pathology C3, Osaka University Graduate School of Medicine, 2 2 Yamadaoka, Suita, Osaka 565 0871, Japan
    Ann Hematol 86:557-64. 2007
    ..2%; p < 0.05). However, GSTP1 promoter hypermethylation was not an independent prognosticator in multivariate analysis. Methylation status of GSTP1 could be an indicator of drug response and a prognosticator for DLBCL...
  24. ncbi Pyrosequencing assays to study promoter CpG site methylation of the O6-MGMT, hMLH1, p14ARF, p16INK4a, RASSF1A, and APC1A genes
    Zarah M Löf-Öhlin
    Department of Clinical Chemistry, Orebro University Hospital, S 70185 Orebro, Sweden
    Oncol Rep 21:721-9. 2009
    ..This approach provides a more comprehensive picture of the distribution of DNA methylation throughout the promoter regions of the studied set of six genes, which will be of benefit in oncological research...
  25. pmc The A/G allele of rs16906252 predicts for MGMT methylation and is selectively silenced in premalignant lesions from smokers and in lung adenocarcinomas
    Shuguang Leng
    Lung Cancer Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108, USA
    Clin Cancer Res 17:2014-23. 2011
    ....
  26. pmc Enhanced 5-methylcytosine detection in single-molecule, real-time sequencing via Tet1 oxidation
    Tyson A Clark
    Pacific Biosciences, 1380 Willow Road, Menlo Park, CA 94025, USA
    BMC Biol 11:4. 2013
    ..We investigated whether conversion of 5-methylcytosine to 5-carboxylcytosine using the enzyme Tet1 would enhance the kinetic signature, thereby improving detection...
  27. ncbi The T genotype of the MGMT C>T (rs16906252) enhancer single-nucleotide polymorphism (SNP) is associated with promoter methylation and longer survival in glioblastoma patients
    K L McDonald
    Prince of Wales Clinical School, University of NSW, Australia
    Eur J Cancer 49:360-8. 2013
    ..An independent validation on larger cohorts is required to confirm the prognostic and predictive value of individuals carrying the T allele...
  28. ncbi IDH1 and IDH2 mutations are prognostic but not predictive for outcome in anaplastic oligodendroglial tumors: a report of the European Organization for Research and Treatment of Cancer Brain Tumor Group
    Martin J van den Bent
    Dept Neuro Oncology and Pathology, Daniel den Hoed Cancer Center and Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
    Clin Cancer Res 16:1597-604. 2010
    ....
  29. ncbi SMAD7 and MGMT genotype variants and cancer incidence in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk Study
    Yet Hua Loh
    MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, United Kingdom
    Cancer Epidemiol 35:369-74. 2011
    ..This exploratory study aims to investigate the association between SMAD7 (rs4464148, rs4939827) and MGMT (rs12917, rs2308321) genotype variants, and all-cancer incidence...
  30. ncbi An analysis of image texture, tumor location, and MGMT promoter methylation in glioblastoma using magnetic resonance imaging
    Sylvia Drabycz
    Department of Electrical and Computer Engineering, University of Calgary, Alberta, Canada
    Neuroimage 49:1398-405. 2010
    ....
  31. ncbi DNA methyltransferases: mechanistic models derived from kinetic analysis
    Ernst G Malygin
    Institute of Molecular Biology, State Research Center of Virology and Biotechnology Vector, Novosibirsk, Russia
    Crit Rev Biochem Mol Biol 47:97-193. 2012
    ..Thus, this review considers in turn studies carried out with the most consistently and extensively investigated [N6-adenine]-, [N4-cytosine]- and [C5-cytosine]-DNA MTases...
  32. ncbi FET-PET assessed recurrence pattern after radio-chemotherapy in newly diagnosed patients with glioblastoma is influenced by MGMT methylation status
    Maximilian Niyazi
    Department of Radiation Oncology, Ludwig Maximilians University Munich, Germany
    Radiother Oncol 104:78-82. 2012
    ....
  33. ncbi MGMT Ile143Val polymorphism, dietary factors and the risk of breast, colorectal and prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study
    Yet Hua Loh
    MRC Centre for Nutritional Epidemiology in Cancer Prevention and Survival, Department of Public Health and Primary Care, University of Cambridge, Worts Causeway, United Kingdom
    DNA Repair (Amst) 9:421-8. 2010
    ..For colorectal cancer, the MGMT Ile143Val polymorphism may confer increased or decreased risk depending on the dietary exposure...
  34. pmc Context-dependent conservation of DNA methyltransferases in bacteria
    Aswin Sai Narain Seshasayee
    National Centre for Biological Sciences, Tata Institute of Fundamental Research, GKVK, Bellary Road, Bangalore 560065, India
    Nucleic Acids Res 40:7066-73. 2012
    ..Despite their sporadic occurrence, conserved R-M systems are present in strength in two highly transformable genera, in which they may contribute to selection against integration of foreign DNA...
  35. pmc MGMT, GATA6, CD81, DR4, and CASP8 gene promoter methylation in glioblastoma
    Daina Skiriute
    Laboratory of Neurooncology and Genetics, Neuroscience Institute, Medical Academy, Lithuanian University of Health Sciences, Eiveniu str, 4, Kaunas, LT, 50009, Lithuania
    BMC Cancer 12:218. 2012
    ..Our aim was to study promoter methylation of newly identified epigenetically silenced genes together with already known epigenetic markers and evaluate its separate and concomitant role in glioblastoma genesis and patient outcome...
  36. pmc Variants of DNA repair genes and the risk of biliary tract cancers and stones: a population-based study in China
    Mingdong Zhang
    Food and Drug Administration, Rockville, Maryland, USA
    Cancer Epidemiol Biomarkers Prev 17:2123-7. 2008
    ..Findings from this population-based study in Shanghai suggest that MGMT gene variants may alter susceptibility to biliary tract cancer, particularly gallbladder cancer. Confirmation in future studies, however, is required...
  37. ncbi MGMT gene promoter methylation as a potent prognostic factor in glioblastoma treated with temozolomide-based chemoradiotherapy: a single-institution study
    Young Suk Kim
    Department of Radiation Oncology, Yonsei University College of Medicine, Yonsei University Health System, Seoul, Korea
    Int J Radiat Oncol Biol Phys 84:661-7. 2012
    ..We evaluated whether hypermethylation of MGMT was associated with survival in patients with glioblastoma multiforme (GBM)...
  38. ncbi Correlation between O6-methylguanine-DNA methyltransferase and survival in elderly patients with glioblastoma treated with radiotherapy plus concomitant and adjuvant temozolomide
    Giuseppe Minniti
    Department of Radiation Oncology, Sant Andrea Hospital, University La Sapienza, Via di Grottarossa 1035, 00189, Rome, Italy
    J Neurooncol 102:311-6. 2011
    ..004 and P = 0.005, respectively). The results of the present study suggest that MGMT methylation status might be an important prognostic factor associated with better OS and PFS in elderly patients with GBM treated with RT and TMZ...
  39. pmc DNA methyltransferase and histone deacetylase inhibitors in the treatment of myelodysplastic syndromes
    Elizabeth A Griffiths
    Sidney Kimmel Comprehensive Cancer Centre, Johns Hopkins Hospital, Baltimore, MD 21231, USA
    Semin Hematol 45:23-30. 2008
    ..Combination therapy offers the possibility of hematologic improvement and remission to myelodysplastic patients with previously untreatable disease...
  40. pmc Hypermethylation of PTGER2 confers prostaglandin E2 resistance in fibrotic fibroblasts from humans and mice
    Steven K Huang
    Department of Internal Medicine, University of Michigan Medical School, 6301 MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109, USA
    Am J Pathol 177:2245-55. 2010
    ....
  41. ncbi Clinical significance of molecular biomarkers in glioblastoma
    C Ang
    Department of Oncology, McGill University and the Segal Cancer Centre Sir Mortimer B Davis Jewish General Hospital, Montreal, Quebec, Canada
    Can J Neurol Sci 37:625-30. 2010
    ..To review the impact of molecular biomarkers on response to therapy and survival in patients with primary glioblastoma (GBM)...
  42. ncbi The promoter hypermethylation status of GATA6, MGMT, and FHIT in glioblastoma
    Gulsah Cecener
    Department of Medical Biology, School of Medicine, Uludag University, Bursa, Turkey
    Cell Mol Neurobiol 32:237-44. 2012
    ..Furthermore, inactivation of FHIT by epigenetic mechanisms in GBM may not be associated with brain tumorigenesis...
  43. ncbi Suppression of intestinal neoplasia by DNA hypomethylation
    P W Laird
    Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142, USA
    Cell 81:197-205. 1995
    ..Our results argue against an oncogenic effect of DNA hypomethylation. Moreover, they are consistent with a role for DNA methyltransferase in the generation of the C to T transitions seen at high frequency in human colorectal tumors...
  44. pmc Comprehensive analysis of MGMT promoter methylation: correlation with MGMT expression and clinical response in GBM
    Nameeta Shah
    The Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment, Swedish Neuroscience Institute, Seattle, Washington, United States of America
    PLoS ONE 6:e16146. 2011
    ..Further prospective validation of these two methods in a large independent patient cohort will be needed to confirm the added value of promoter wide analysis of MGMT methylation in the clinical setting...
  45. pmc Absence of the MGMT protein as well as methylation of the MGMT promoter predict the sensitivity for temozolomide
    K A van Nifterik
    Department of Radiation Oncology, VU University Medical Center, P O Box 7057, Amsterdam 1007 MB, The Netherlands
    Br J Cancer 103:29-35. 2010
    ....
  46. ncbi DNA methylation and gene silencing in cancer
    Stephen B Baylin
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    Nat Clin Pract Oncol 2:S4-11. 2005
    ..This review examines alteration in DNA methylation in cancer, effects on gene expression, and implications for the use of hypomethylating agents in the treatment of cancer...
  47. pmc Foamy combinatorial anti-HIV vectors with MGMTP140K potently inhibit HIV-1 and SHIV replication and mediate selection in vivo
    H P Kiem
    Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA 98109 1024, USA
    Gene Ther 17:37-49. 2010
    ....
  48. pmc Correlation of MGMT promoter methylation status with gene and protein expression levels in glioblastoma
    Miyuki Uno
    Department of Neurology, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
    Clinics (Sao Paulo) 66:1747-55. 2011
    ....
  49. ncbi Chemoradiotherapy of newly diagnosed glioblastoma with intensified temozolomide
    Markus Weiler
    Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tubingen, Tubingen, Germany
    Int J Radiat Oncol Biol Phys 77:670-6. 2010
    ..To evaluate the toxicity and efficacy of chemoradiotherapy with temozolomide (TMZ) administered in an intensified 1-week on/1-week off schedule plus indomethacin in patients with newly diagnosed glioblastoma...
  50. ncbi Frequent hypermethylation of the DNA repair gene MGMT in long-term survivors of glioblastoma multiforme
    Ramon Martinez
    J Neurooncol 83:91-3. 2007
    ..The methylation rate in LTS GBM was significantly higher (77.8% vs. 39.2%, P = 0.033) which suggests that MGMT hypermethylation is a frequent hallmark of LTS GBM and contributes to characterize this intriguing GBM subtype...
  51. ncbi RASSF1A, BLU, NORE1A, PTEN and MGMT expression and promoter methylation in gliomas and glioma cell lines and evidence of deregulated expression of de novo DNMTs
    Aiala Lorente
    Brain Tumor Biology Unit, University of Navarra, Irunlarrea 1, Pamplona, Spain
    Brain Pathol 19:279-92. 2009
    ..No association between methylation and loss of expression could be established for PTEN. We identified de novo DNMTs overexpression in a subset of tumors which may explain the methylation phenotype of individual gliomas...
  52. pmc Direct interaction between DNA methyltransferase DIM-2 and HP1 is required for DNA methylation in Neurospora crassa
    Shinji Honda
    Institute of Molecular Biology, University of Oregon, Eugene, OR 97403 1229, USA
    Mol Cell Biol 28:6044-55. 2008
    ....
  53. ncbi MGMT promoter methylation in malignant gliomas: ready for personalized medicine?
    Michael Weller
    Department of Neurology, University Hospital Zurich, Frauenklinikstrasse 26, Zurich, Switzerland
    Nat Rev Neurol 6:39-51. 2010
    ..Moreover, future clinical trials will need to determine, for each subtype of glioma, the degree to which MGMT promoter methylation is predictive or prognostic, and whether testing should become routine clinical practice...
  54. pmc O(6)-methylguanine DNA-methyltransferase methylation status can change between first surgery for newly diagnosed glioblastoma and second surgery for recurrence: clinical implications
    Alba A Brandes
    Department of Medical Oncology, Azienda USL Bellaria Maggiore Hospital, Bologna, Italy
    Neuro Oncol 12:283-8. 2010
    ..MGMT methylation status determined at first surgery appears to be of prognostic value; however, it is not predictive of outcome following second surgery...
  55. pmc MGMT promoter methylation is prognostic but not predictive for outcome to adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors: a report from EORTC Brain Tumor Group Study 26951
    Martin J van den Bent
    Department of Neuro Oncology and Pathology, Daniel den Hoed Cancer Center and Erasmus University Medical Center, Rotterdam, The Netherlands
    J Clin Oncol 27:5881-6. 2009
    ..It is unknown if MGMT promoter methylation is also predictive to outcome to RT followed by adjuvant procarbazine, lomustine, and vincristine (PCV) chemotherapy in patients with anaplastic oligodendroglial tumors (AOT)...
  56. pmc Sequence-specific modification of mitochondrial DNA using a chimeric zinc finger methylase
    Michal Minczuk
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom
    Proc Natl Acad Sci U S A 103:19689-94. 2006
    ..This is a proof of principle that it is possible to target and alter mtDNA in a sequence-specific manner by using zinc finger technology...
  57. ncbi Sensitization for death receptor- or drug-induced apoptosis by re-expression of caspase-8 through demethylation or gene transfer
    S Fulda
    University Children's Hospital, Prittwitzstr. 43, D-89075 Ulm, Germany
    Oncogene 20:5865-77. 2001
    ..g. by demethylation or caspase-8 gene transfer, might be an effective strategy to restore sensitivity for chemotherapy- or death receptor-induced apoptosis in various tumors in vivo...
  58. pmc Identification of DNMT1 (DNA methyltransferase 1) hypomorphs in somatic knockouts suggests an essential role for DNMT1 in cell survival
    Gerda Egger
    Norris Comprehensive Cancer Center, Departments of Urology and Biochemistry and Molecular Biology, Keck School of Medicine, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90089, USA
    Proc Natl Acad Sci U S A 103:14080-5. 2006
    ..Our data suggest that DNMT1 might be essential for maintenance of DNA methylation, proliferation, and survival of cancer cells...
  59. ncbi Anti-O6-methylguanine-methyltransferase (MGMT) immunohistochemistry in glioblastoma multiforme: observer variability and lack of association with patient survival impede its use as clinical biomarker
    Matthias Preusser
    Department of Internal Medicine 1, Medial University of Vienna, Vienna, Austria
    Brain Pathol 18:520-32. 2008
    ..In our hands, observer variability as well as lack of association with the MGMT promoter methylation status and patient survival impeded the use of anti-MGMT immunohistochemistry as a clinical biomarker for routine diagnostic purposes...
  60. ncbi Application of DNA methyltransferases in targeted DNA methylation
    Albert Jeltsch
    Biochemistry Laboratory, School of Engineering and Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany
    Appl Microbiol Biotechnol 75:1233-40. 2007
    ..Thereby, gene expression can be switched off specifically, efficiently, and stably, which has a number of potential medical applications...
  61. ncbi Clinical correlation of MGMT protein expression and promoter methylation in Chinese glioblastoma patients
    Kai Tang
    Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No 6 Tiantan Xili 100050, Dongcheng District, Beijing, China
    Med Oncol 29:1292-6. 2012
    ....
  62. pmc O6-Methylguanine DNA methyltransferase protein expression in tumor cells predicts outcome of temozolomide therapy in glioblastoma patients
    Sabine Spiegl-Kreinecker
    Department of Neurosurgery, Wagner Jauregg Hospital, Wagner Jauregg Weg 15, 4020 Linz, Austria
    Neuro Oncol 12:28-36. 2010
    ..00, 95% CI 0.45-2.20; P = .99). These data suggest that lack of MGMT protein expression is superior to promoter methylation as a predictive marker for TMZ response in GBM patients...
  63. pmc The structural basis of differential DNA sequence recognition by restriction-modification controller proteins
    N J Ball
    Biomolecular Structure Group, Institute of Biomedical and Biomolecular Sciences, School of Biological Sciences, University of Portsmouth, Portsmouth PO1 2DY, UK
    Nucleic Acids Res 40:10532-42. 2012
    ....
  64. ncbi Activation of the p53 DNA damage response pathway after inhibition of DNA methyltransferase by 5-aza-2'-deoxycytidine
    A R Karpf
    Division of Molecular Pharmacology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA
    Mol Pharmacol 59:751-7. 2001
    ..Our data raise the hypothesis that p53 activation may contribute to the clinical efficacy and/or toxicity of 5-aza-CdR...
  65. pmc Purification and characterisation of a novel DNA methyltransferase, M.AhdI
    Phil Marks
    Biophysics Laboratories, Institute of Biomedical and Biomolecular Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK
    Nucleic Acids Res 31:2803-10. 2003
    ..AhdI appears to be a novel R-M system with properties intermediate between simple type II systems and more complex type I systems, and may represent an intermediate in the evolution of R-M systems...
  66. ncbi MGMT CpG island is invariably methylated in adult astrocytic and oligodendroglial tumors with IDH1 or IDH2 mutations
    Shani Mulholland
    Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Addenbrooke s Hospital, Cambridge, United Kingdom
    Int J Cancer 131:1104-13. 2012
    ..We suggest that MGMT methylation may be one of the earliest events in the development of astrocytic and oligodendroglial tumors...
  67. ncbi Screening for compounds that modulate epigenetic regulation of the transcriptome: an overview
    Richard M Eglen
    Corning Life Sciences, Corning, NY 14831, USA
    J Biomol Screen 16:1137-52. 2011
    ..This review focuses on the rationale for drug development of these enzymes, as well the utility of HTS methods used in identifying and optimizing novel selective compounds that modulate epigenetic control of the human transcriptome...
  68. pmc Investigation of MGMT and DAPK1 methylation patterns in diffuse large B-cell lymphoma using allelic MSP-pyrosequencing
    Lasse Sommer Kristensen
    Department of Hematology, Rigshospitalet, Copenhagen, Denmark
    Sci Rep 3:2789. 2013
    ..04), and DAPK1 methylation of the A-allele was associated with shorter overall survival (p-value=0.006). In future cancer research allelic MSP-pyrosequencing may be used to study a wide range of other loci...
  69. ncbi MDR1 promoter hypermethylation in MCF-7 human breast cancer cells: changes in chromatin structure induced by treatment with 5-Aza-cytidine
    Gloria L David
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland 21231 1000, USA
    Cancer Biol Ther 3:540-8. 2004
    ..In this state, MDR1 expression was markedly sensitive to treatment with the histone deacetylase inhibitor trichostatin A...
  70. ncbi Methylation of MGMT in malignant pleural mesothelioma occurs in a subset of patients and is associated with the T allele of the rs16906252 MGMT promoter SNP
    Lasse Sommer Kristensen
    Institute of Human Genetics, Aarhus University, The Bartholin Building, Wilhelm Meyers Allé 4, DK 8000 Aarhus C, Denmark
    Lung Cancer 71:130-6. 2011
    ..In conclusion, methylation of the MGMT promoter occurs in a subset of MPM patients and is associated with the T allele of the MGMT rs16906252 SNP. However, complete silencing of MGMT in MPM is a rare event...
  71. ncbi Promoter hypermethylation of RASSF1A, MGMT, and HIC-1 genes in benign and malignant colorectal tumors
    Hamdy E Abouzeid
    Radio Biological Applications Department, Nuclear Research Center, Atomic Energy Authority, Cairo, Egypt corrected
    Tumour Biol 32:845-52. 2011
    ..Hypermethylation of MGMT and HIC-1 genes plays an important role in the initiation of disease especially ulcerative colitis-carcinoma pathway...
  72. ncbi Polymorphisms in MGMT and DNA repair genes and the risk of esophageal adenocarcinoma
    James Doecke
    Queensland Institute of Medical Research, Brisbane, Queensland, Australia
    Int J Cancer 123:174-80. 2008
    ..In summary, MGMT SNPs are associated with increased risks of EAC. Exposure to acid reflux, and possibly smoking, confer markedly higher risks among homozygous variant genotype carriers...
  73. pmc Polymorphisms of the DNA repair gene MGMT and risk and progression of head and neck cancer
    Zhengdong Zhang
    Department of Epidemiology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    DNA Repair (Amst) 9:558-66. 2010
    ....
  74. pmc MGMT promoter methylation is predictive of response to radiotherapy and prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma
    Andreana L Rivera
    Departments of Pathology and Radiation Oncology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 0097, Houston, TX 77030, USA
    Neuro Oncol 12:116-21. 2010
    ..Since this biomarker has also been shown to predict response to alkylating agents, perhaps MGMT promoter methylation represents a general, favorable prognostic factor in GBM...
  75. pmc MGMT promoter methylation in gliomas-assessment by pyrosequencing and quantitative methylation-specific PCR
    Annette Bentsen Håvik
    Section for Cancer Cytogenetics, Institute for Medical Informatics, Oslo University Hospital The Norwegian Radium Hospital, P, O, Box 4950 Nydalen, N 0424 Oslo, Norway
    J Transl Med 10:36. 2012
    ..However, reported methylation frequencies vary significantly partly due to lack of consensus in the choice of analytical method...
  76. pmc The methylomes of six bacteria
    Iain A Murray
    New England Biolabs, 240 County Road, Ipswich, MA 01938, USA
    Nucleic Acids Res 40:11450-62. 2012
    ....
  77. ncbi Epigenetic therapy in cancer: molecular background and clinical development of histone deacetylase and DNA methyltransferase inhibitors
    Regine Schneider-Stock
    Department of Medicine 1, University Hospital Erlangen, Ulmenweg 18, 91054 Erlangen, Germany
    IDrugs 10:557-61. 2007
    ..In addition, inhibitors of HDAC and DNMT possess direct cytotoxic properties, and can sensitize tumor cells to conventional radiotherapy and chemotherapy...
  78. ncbi Low-dose fotemustine for recurrent malignant glioma: a multicenter phase II study
    Alessandra Fabi
    Division of Medical Oncology, Regina Elena Cancer Institute, Via Elio Chianesi, 53, Rome, Italy
    J Neurooncol 100:209-15. 2010
    ..The role of MGMT gene promoter methylation status in relation to sensitivity to fotemustine is still unclear and needs further evaluation in future clinical trials...
  79. pmc Chemical decomposition of 5-aza-2'-deoxycytidine (Decitabine): kinetic analyses and identification of products by NMR, HPLC, and mass spectrometry
    Daniel K Rogstad
    Department of Basic Sciences, Loma Linda University School of Medicine, Alumni Hall for Basic Science, Room 101, 11021 Campus Street, Loma Linda, California 92350, USA
    Chem Res Toxicol 22:1194-204. 2009
    ..The results reported here will facilitate ongoing studies and clinical trials aimed at understanding the mechanisms of action, toxicity, and possible mutagenicity of DAC and related analogues...
  80. pmc High specificity of quantitative methylation-specific PCR analysis for MGMT promoter hypermethylation detection in gliomas
    Paola Parrella
    Oncology Laboratory, IRCCS Casa Sollievo della Sofferenza Hospital, 71013 San Giovanni Rotondo, Italy
    J Biomed Biotechnol 2009:531692. 2009
    ..Our results suggest that QMSP analysis may represent a powerful tool to identify glioma patients that will benefit from alkylating agents chemotherapy...
  81. ncbi Temozolomide three weeks on and one week off as first line therapy for patients with recurrent or progressive low grade gliomas
    A Tosoni
    Department of Medical Oncology, Bellaria Maggiore Hospital, Via Altura 3, 40139, Bologna, Italy
    J Neurooncol 89:179-85. 2008
    ..Patients with recurrent or progressive low grade gliomas survive for a decade or more following diagnosis, and may be at a higher risk for treatment-related complications, such as cognitive impairment from radiotherapy...
  82. pmc Role of the Campylobacter jejuni Cj1461 DNA methyltransferase in regulating virulence characteristics
    Joo Sung Kim
    Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912, USA
    J Bacteriol 190:6524-9. 2008
    ..Electron microscopy revealed that the mutant strain had flagella but with aberrant structure. The Deltacj1461 mutant was sevenfold more adherent to but 50-fold less invasive of INT-407 human epithelial cells than the wild type...
  83. pmc Targeted DNA methylation by a DNA methyltransferase coupled to a triple helix forming oligonucleotide to down-regulate the epithelial cell adhesion molecule
    Bernardina T F van der Gun
    Epigenetic Editing, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands
    Bioconjug Chem 21:1239-45. 2010
    ....
  84. pmc Phasevarion mediated epigenetic gene regulation in Helicobacter pylori
    Yogitha N Srikhanta
    Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia
    PLoS ONE 6:e27569. 2011
    ..pylori. Characterisation of H. pylori modH phasevarions to define stable immunological targets will be essential for vaccine development and may also contribute to understanding H. pylori pathogenesis...
  85. ncbi Fixation of brain tumor biopsy specimens with RCL2 results in well-preserved histomorphology, immunohistochemistry and nucleic acids
    Matthias Preusser
    Department of Medicine I, Medical University of Vienna, Vienna, Austria
    Brain Pathol 20:1010-20. 2010
    ..In conclusion, RCL2 fixation of brain tumor biopsies does not seem to significantly compromise histological tumor typing or immunohistochemistry and preserves nucleic acids (DNA and RNA) at a better quality than formalin fixation...
  86. ncbi DNA methylation in states of cell physiology and pathology
    Anetta Sulewska
    Department of Thoracic Surgery, Medical University of Bialystok, Poland
    Folia Histochem Cytobiol 45:149-58. 2007
    ..With the application of the Real-Time PCR technique (using primers for methylated and unmethylated sequences) five new genes which are potential biomarkers of lung cancer have been presented...
  87. ncbi Diversity of DNA methyltransferases that recognize asymmetric target sequences
    Urulangodi Kunhiraman Madhusoodanan
    Department of Biochemistry, Indian Institute of Science, Bangalore, India
    Crit Rev Biochem Mol Biol 45:125-45. 2010
    ..The rapid progress made by the genome sequencing of bacteria and archaea may accelerate the identification and study of species- and strain-specific MTases of host-adapted bacteria and their roles in pathogenic mechanisms...
  88. ncbi Relevance of MSP assay for the detection of MGMT promoter hypermethylation in glioblastomas
    Kazunari Yachi
    Department of Neurological Surgery, Nihon University School of Medicine, Tokyo 173 8610, Japan
    Int J Oncol 33:469-75. 2008
    ..In all of the cell lines with loss of MGMT expression, signals of methylated DNA were detected by MSP. Our data support the feasibility and reliability of MSP analysis, which could be routinely implemented in the diagnostic setting...
  89. pmc The methyltransferase from the LlaDII restriction-modification system influences the level of expression of its own gene
    Lisa Lystbaek Christensen
    Department of Dairy and Food Science, Centre of Advanced Food Studies, The Royal Veterinary and Agricultural University, DK 1958 Frederiksberg C, Denmark
    J Bacteriol 186:287-95. 2004
    ..No regulation was found for llaDIIR, which appears to be constitutively expressed...
  90. pmc The human colon cancer methylome shows similar hypo- and hypermethylation at conserved tissue-specific CpG island shores
    Rafael A Irizarry
    Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA
    Nat Genet 41:178-86. 2009
    ....
  91. ncbi MGMT methylation: a marker of response to temozolomide in low-grade gliomas
    Sibille Everhard
    Institut National de la Sante et de la Recherche Medicale, U711, Paris, France
    Ann Neurol 60:740-3. 2006
    ..0001). Assessment of MGMTP status could help identifying low-grade gliomas patients more likely to respond to chemotherapy or to benefit from MGMT depletion strategies...
  92. pmc O6-methylguanine-DNA methyltransferase deficiency in developing brain: implications for brain tumorigenesis
    Michael S Bobola
    Department of Neurological Surgery, Box 356470, University of Washington, Seattle, WA 98195 6470, USA
    DNA Repair (Amst) 6:1127-33. 2007
    ..Our findings provide possible mechanistic insight into epidemiologic data associating maternal alkylating agent exposure with brain tumor incidence...
  93. pmc Haemophilus influenzae phasevarions have evolved from type III DNA restriction systems into epigenetic regulators of gene expression
    Kate L Fox
    School of Molecular and Microbial Sciences, University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia
    Nucleic Acids Res 35:5242-52. 2007
    ..These data suggest that evolution of this type III R-M system into an epigenetic mechanism for controlling gene expression has, in some strains, resulted in loss of the DNA restriction function...
  94. ncbi Pitfalls in the assessment of MGMT expression and in its correlation with survival in diffuse astrocytomas: proposal of a feasible immunohistochemical approach
    David Capper
    Institute of Brain Research, University of Tubingen, Tubingen, Germany
    Acta Neuropathol 115:249-59. 2008
    ....
  95. pmc Serum DNA can define tumor-specific genetic and epigenetic markers in gliomas of various grades
    Iris Lavon
    Gaffin Center for Neuro Oncology and the Department of Neurology, Hadassah Hebrew University Medical Center, Ein Kerem, PO Box 12000, Jerusalem 91120, Israel
    Neuro Oncol 12:173-80. 2010
    ..The sensitivity is moderate and specificity is high for both low- and high-grade tumors. Future studies should identify a panel of biomarkers that bear the highest potential for clinical application...
  96. ncbi Current therapeutic paradigms in glioblastoma
    Allison Quick
    Department of Radiation Oncology, Ohio State University, Madison, WI, 53792, USA
    Rev Recent Clin Trials 5:14-27. 2010
    ..This article will review the current therapies for GBM and the investigation of new molecular and targeted therapies, such as EGFR inhibitors, mTOR/PI3Kinase inhibitors, and anti-angiogenesis agents...
  97. pmc DNA repair modulates the vulnerability of the developing brain to alkylating agents
    G E Kisby
    Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, Portland, OR 97239, United States
    DNA Repair (Amst) 8:400-12. 2009
    ....
  98. pmc Methylation-sensitive high resolution melting (MS-HRM): a new approach for sensitive and high-throughput assessment of methylation
    Tomasz K Wojdacz
    Molecular Pathology Research Laboratory, Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
    Nucleic Acids Res 35:e41. 2007
    ..The simplicity and high reproducibility of the MS-HRM protocol makes MS-HRM the method of choice for methylation assessment in many diagnostic and research applications...
  99. ncbi MGMT prognostic impact on glioblastoma is dependent on therapeutic modalities
    Emmanuelle Criniere
    INSERM, U711, Biologie des Interactions Neurones and Glie, Universite Pierre et Marie Curie, Faculte de Medecine, Paris, France
    J Neurooncol 83:173-9. 2007
    ..001). This suggests that the prognostic impact of MGMT methylation is dependent on therapeutic modalities and schedules. MGMT methylation was not correlated with the main molecular alterations, such as 10q loss and p53 expression...
  100. ncbi Epi-drugs to fight cancer: from chemistry to cancer treatment, the road ahead
    Antonello Mai
    Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Universita di Roma, 00185 Roma, IT, Italy
    Int J Biochem Cell Biol 41:199-213. 2009
    ..In this review we will focus on the chemical aspects of such molecules, joined to their effective (or potential) application in cancer therapy...
  101. ncbi Intratumoral homogeneity of MGMT promoter hypermethylation as demonstrated in serial stereotactic specimens from anaplastic astrocytomas and glioblastomas
    Eva M Grasbon-Frodl
    Center for Neuropathology and Prion Research, Ludwig Maximilians Universitat Munchen, Munich, Germany
    Int J Cancer 121:2458-64. 2007
    ..The methylation profile, as defined by MSP and sodium bisulfite sequencing, constitutes a homogeneous marker throughout malignant gliomas. The lack of correlation between MGMT status and MGMT protein expression needs further evaluation...

Research Grants66

  1. Diet and DNA methylation in colon mucosa and adenomas
    Jean Pierre Issa; Fiscal Year: 2007
    ..These studies should provide definitive information on interactions between diet and DNA methylation in human colorectal mucosa and cancer. [unreadable] [unreadable]..
  2. Neoplasia and Methylated CpG Islands Amplification
    Jean Pierre Issa; Fiscal Year: 2004
    ..Ultimately, methylation profiling may prove very valuable in identifying subsets of patients with distinct clinical courses and response to specific therapeutic interventions, including using methylation inhibitors. ..
  3. DNA Methylation in Colon Cancer Metastasis
    Jean Pierre Issa; Fiscal Year: 2008
    ..abstract_text> ..
  4. METHYLATION PROFILING IN COLORECTAL CANCER
    Jean Pierre Issa; Fiscal Year: 2003
    ..Ultimately, this work aims at establishing that methylation profiling may carry the same clinical implications as that already established for genetic profiling in neoplasia. ..
  5. A universal DNA endonuclease
    Shuang yong Xu; Fiscal Year: 2005
    ..For isothermal applications of the universal nuclease at 50oC-70oC, the nuclease domain will be derived from thermophilic endonucleases. ..
  6. Cloning and Engineering of Nicking enzymes
    Shuang yong Xu; Fiscal Year: 2004
    ..abstract_text> ..
  7. CANCER AND LEUKEMIA GROUP B--MOUNT SINAI
    Lewis Silverman; Fiscal Year: 2002
    ..With these associated investigators in 12 affiliated institutions, Mount Sinai plans to participate in all Group activities. ..
  8. Engineering DNA nicking endonucleases
    Shuang yong Xu; Fiscal Year: 2006
    ..Under Phase II funding, this isothermal amplification method (NEMDA) will be optimized and the sensitivity will be improved. Finally, we will investigate the potential of NEMDA for detections of pathogens and its use in bio-prospecting. ..
  9. A Genetic System Able to Screen for Active DNA Demethylation
    Shuang yong Xu; Fiscal Year: 2006
    ..In addition, knowledge of the mechanism of demethylation could be crucial in converting fully differentiated adult stem cells into totipotent stem cells. [unreadable] [unreadable] [unreadable]..
  10. Genomic & Genetic Characterization of Amplicons in GBMs
    Lynda Chin; Fiscal Year: 2007
    ..The highest potential candidate glioma oncogene will be further validated by rigorous in vivo transgenesis study. ..
  11. Reactivation Methylation-Silenced Genes by Polyphenols
    Chung Yang; Fiscal Year: 2007
    ..5. To determine whether EGCG, alone or in combination with other agents, can prevent hypermethylation of genes and tumor development in the intestinal tumorigenesis model in the Min mice. ..
  12. ESOPHAGEAL ADENOCARCINOGENESIS AND ITS PREVENTION
    Chung Yang; Fiscal Year: 2007
    ..These studies are expected to fully elucidate the roles of oxidative stress and aberrant AA metabolism in the formation of EAC and help develop effective agents for its prevention. ..
  13. REGULATION OF FOLATE CATABOLISM
    PATRICK STOVER; Fiscal Year: 2007
    ..2). to determine the risk that folate catabolism contributes to folate-associated pathologies. (3). to establish relationships between catecholamines and folate metabolism. ..
  14. Phase I trial of PHP with high-dose IL-2
    Wolfram Samlowski; Fiscal Year: 2006
    ..abstract_text> ..
  15. DNA Methylation, Chromatin, and Globin Gene Silencing
    Joseph DeSimone; Fiscal Year: 2006
    ..These studies will define the mechanisms of gamma-globin gene silencing, and will aid in the development of new procedures to augment HbF production in patients with sickle cell disease. ..
  16. H.pylori Effects on DNA Repair in Gastric Epithelium
    Antonia Sepulveda; Fiscal Year: 2008
    ..Knowledge gained from this study is likely to support the indication for Hp eradication in H. pylori-infected patients to prevent GC. [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]..
  17. Chicago Sickle Cell Clinical Network
    Joseph DeSimone; Fiscal Year: 2008
    ..To determine if there is a genetic basis for treatment variation, we will evaluate patients for genotypic variability using a number of polymorphic genes, such as mu receptor, MDR1 protein, and cytochrome 2D6. ..
  18. Silencing of transposons in mammalian germ cells
    Timothy Bestor; Fiscal Year: 2008
    ..The studies described here are almost certain to identify factors that regulate de novo methylation in the male germ line. [unreadable] [unreadable] [unreadable]..
  19. INVESTIGATIONS OF MAMMALIAN AMINOPROPYLTRANSFERASES
    ANTHONY PEGG; Fiscal Year: 2009
    ..abstract_text> ..
  20. Homeostatic Regulation of Folate Metabolism
    Patrick J Stover; Fiscal Year: 2010
    ..5. regulation of cSHMT by folate/choline preserves dTMP pools at the expense of AdoMet synthesis. The long-term goals of this project are: 1. to define homeostatic mechanisms used bv cells to regulate folate metabolism. ..
  21. Regulatory Functions of APE1 - An Essential Repair Protein
    Sankar Mitra; Fiscal Year: 2010
    ..Furthermore, our studies should help identify APE1-regulated key signaling pathways in tumor induction and promotion which could be potential targets for cancer therapy. ..
  22. TUMOR SUPPRESSOR GENE METHYLATION IN LUNG ADENOCARCINOMA
    Steven A Belinsky; Fiscal Year: 2010
    ..Transient transfection of minimized promoters into cell lines with an endogenously active or silenced gene will be used to elucidate the sequence of changes involved in repression of promoter activity. REVISED: July 7, 2005 ..
  23. Mechanism of combined 'epigenetic therapy' in myeloid malignancies
    Steven Gore; Fiscal Year: 2009
    ....
  24. Gene therapy for Fanconi anemia
    Hans Peter Kiem; Fiscal Year: 2009
    ..Our ultimate goal is to improve or cure the hematopoietic symptoms in FA patients by lentivirus-mediated HSC gene transfer, and develop methodologies that would be applicable to other genetic disorders and hematological diseases. ..
  25. Developmental pathways, cancer, and DNA hypermethylation
    Stephen Baylin; Fiscal Year: 2009
    ..Animal models will then be utilized to extrapolate our results to in vivo tumor progression settings. ..
  26. Phase I study of 5-aza-2?-deoxycitidine in acute lymphocytic leukemia
    Guillermo Garcia Manero; Fiscal Year: 2008
    ..In this proposal, we plan to develop a new form of low-dose chemotherapy, decitabine, for these patients. Early results indicate that this is active and safe. [unreadable] [unreadable] [unreadable]..
  27. 2008 FASEB Summer Research Conference on Biological Methylation: from DNA to Hist
    Xiaodong Cheng; Fiscal Year: 2008
    ..In addition, three afternoon mini-symposia are devoted to young investigators. [unreadable] [unreadable] [unreadable] [unreadable]..
  28. High throughput profiling of genomic methylation patterns
    Timothy Bestor; Fiscal Year: 2008
    ..We introduce new technologies that will profile the methylation pattern of the entire genome as a means to identify methylation pattern abnormalities that are associated with human breast cancer. [unreadable] [unreadable] [unreadable]..
  29. Early cellular immune responses to EBV
    Sumita Bhaduri McIntosh; Fiscal Year: 2008
    ..It is also expected to enhance the understanding of EBV lymphoproliferative diseases and have potential diagnostic and therapeutic implications. [unreadable] [unreadable]..
  30. Zeiss Meta 510 Confocal Imaging System
    Judith Christman; Fiscal Year: 2006
    ..unreadable] [unreadable] [unreadable]..
  31. DNA ADDUCTS FORMED DURING BRAIN TUMOR THERAPY
    William Bodell; Fiscal Year: 2001
    ..Number of treatment. These studies will be the first to investigate the formation of BCNU derived DNA abducts in a ic. Brain tumor model. ..
  32. FASEB Summer Conference: Folate, B12 and 1C Metabolism
    PATRICK STOVER; Fiscal Year: 2004
    ..Similarly, the poster sessions also highlight the activities and needs of the younger participants. ..
  33. MARKERS FOR LUNG CARCINOGENESIS IN BRONCHIAL EPITHELIUM
    Steven Belinsky; Fiscal Year: 2001
    ..f., simply markers of exposure) and help identify genetic alterations that are candidate markers of respiratory carcinogenesis. ..
  34. Hematopoietic Potential of Muscle-Derived Cells
    Hans Peter Kiem; Fiscal Year: 2004
    ..abstract_text> ..
  35. FSHD Syndrome: DNA Repeats, Methylation, & Chromatin
    Melanie Ehrlich; Fiscal Year: 2003
    ..The proposed research should help elucidate the molecular etiology of the enigmatic FSHD syndrome. ..
  36. ENYZMES AFFECTING THE ACCUMULATION OF ALTERED PROTEINS
    Steven Clarke; Fiscal Year: 2003
    ..These studies will hopefully not only provide a new window to view protein life but may also suggest that the biological aging process may be closely linked to how well cells can keep polypeptides free of spontaneous covalent damage. ..
  37. Methylation Landscape of the Human Genome
    Timothy Bestor; Fiscal Year: 2003
    ..The impending completion of the sequence of the human genome presents a unique opportunity to gain understanding of the shape of genomic methylation patterns and their role in human development and disease. ..
  38. MOLECULAR PATHOGENESIS OF MALIGNANT MELANOMA
    Lynda Chin; Fiscal Year: 2002
    ....
  39. DNA METHYLTRANSFERASE/HISTONE DEACETYLASE INHIBITION
    Steven Gore; Fiscal Year: 2002
    ..This will enable determination of the "molecular response rate" to this therapy and preliminary exploration of correlation between these molecular endpoints and clinical response. ..
  40. HIGH THROUGHPUT METHYLATION ANALYSIS IN CANCER
    Tim Huang; Fiscal Year: 2002
    ..Moreover, the characterization of the corresponding biological relevant cDNAs will open unforeseen avenues for investigating the pathology of cancer and for better treatment of the disease. ..
  41. MECHANISTIC STUDIES ON TEA AND CARCINOGENESIS
    Chung Yang; Fiscal Year: 2005
    ..The applicant and colleagues will address key issues concerning the bioavailability and bioactivities of O-methyl, glucuronide, and sulfate derivatives and two ring-fission metabolites of tea catechins. ..
  42. Phase1/11 study of 5-aza-2'-deoxycytidine and valproic *
    Guillermo Garcia Manero; Fiscal Year: 2005
    ..Decitabine will be generously provided by SuperGen (r). Valproic acid is an FDA approved anti-convulsant. ..
  43. Cell Cycle Controlling Genes in Adult Acute Lymphoma
    Guillermo Garcia Manero; Fiscal Year: 2005
    ..abstract_text> ..
  44. Epigenetic Biomarkers for Ovarian Cancer Progression
    Tim Huang; Fiscal Year: 2005
    ..Additionally, the study will give insights into the role of CpG island hypermethylation in drug-resistant ovarian cancer. ..
  45. Gene Methylation and Therapeutic Response in Lung Cancer
    Steven Belinsky; Fiscal Year: 2005
    ..The validation of these genes as biomarkers of lung cancer risk and their detection in sputum and/or serum could ultimately support chemoprevention trials for preventing lung cancer. ..
  46. 5-Azacytidine and MS-275 in Myeloid Malignancies
    Steven Gore; Fiscal Year: 2005
    ..abstract_text> ..
  47. NOVEL DNA METHYLTRANSFERASES IN DEVELOPMENT AND DISEASE
    Timothy Bestor; Fiscal Year: 2002
    ..abstract_text> ..
  48. The Environment and Epigenetic Gene Silencing in Cancer
    Stephen Baylin; Fiscal Year: 2009
    ..These, in turn, may be driven, and/or modulated, by key environmental factors. Thus, it is inferred that a key to cancer prevention may be to induce reversal of, or block, epigenetic gene silencing. ..
  49. NABTT-Consortium Therapeutic Studies of CNS Malignancies
    Stuart Grossman; Fiscal Year: 2008
    ..abstract_text> ..
  50. DeNovo DNA Methyltransferases as Anticancer Drug Targets
    Judith Christman; Fiscal Year: 2002
    ..2) Use a novel SDS-PAGE gel assay that measures inhibitor binding affinity for DNMTs to predict the potency of a variety of new inhibitory targets for DNMTs 1, 3a and 3b. ..
  51. Folic Acid Enhances Repair Mechanism in the Adult CNS
    Bermans J Iskandar; Fiscal Year: 2010
    ....
  52. Enigmatic Mammalian DNA Methyltransferase Homologue
    Timothy Bestor; Fiscal Year: 2006
    ..We will perform biochemical and genetic experiments that will determine the biological functions of Dnmt2 in normal cells, and will determine whether the Dnmt2 gene is altered in neoplastic diseases of humans. ..
  53. FSHD: Chromatin Structure, Looping, & Expression
    Melanie Ehrlich; Fiscal Year: 2009
    ..The proposed research should elucidate new aspects of long-distance control of gene expression as well as lending clinically useful insights into this currently intractable disease. ..
  54. Gene Transfer to Facilitate Dose-Intensification in the Treatment of Pediatric B*
    Lars Wagner; Fiscal Year: 2007
    ..We hypothesize this strategy will be well tolerated and allow for meaningful dose escalation through chemoprotection afforded by gene transfer into hematopoietic stem cells. [unreadable] [unreadable] [unreadable]..
  55. Cord Blood Expansion and Transplantation in a Nonhuman Primate Model
    Hans Peter Kiem; Fiscal Year: 2009
    ....
  56. INTEGRIN ANTAGONISTS IN GLIOMA BIOLOGY, IMAGING, THERAPY
    Tom Mikkelsen; Fiscal Year: 2003
    ..abstract_text> ..
  57. MGMT-Mediated in vivo Selection in a Large Animal Model
    Hans Peter Kiem; Fiscal Year: 2006
    ..These experiments will provide a platform for studies using gene-modified allogeneic stem cells to improve nonmyeloablative transplant strategies. ..
  58. DNA Adducts Formed by Dopamine
    William Bodell; Fiscal Year: 2004
    ..In addition, the results of these studies will provide unique molecular markers that will be used in future studies to evaluate whether this process is occurring in the substantia nigra of human brain. ..
  59. Changes in Tumor DNA Methylation with Decitabine
    David Stewart; Fiscal Year: 2006
    ..This preliminary look at individual genes may provide a molecular rationale for future decitabine therapeutic studies in specific relevant tumor types. ..
  60. NEW APPLICATIONS IN BRAIN TUMOR THERAPY
    Tom Mikkelsen; Fiscal Year: 2008
    ..These efforts speak to the ultimate goal of our group and NABTT Consortium: improving the outcome of brain tumor patients. ..
  61. MOLECULAR GLIOMA THERAPIES AND DIAGNOSTICS
    Tom Mikkelsen; Fiscal Year: 2004
    ..abstract_text> ..
  62. A MULTI-USE GLIOMA BIOREPOSITORY
    Tom Mikkelsen; Fiscal Year: 2006
    ..We seek support to expand this multi-use glioma biorepository into an ongoing resource of the best characterized glioma material with clinical correlative and genomic data available. ..
  63. Genomics Screening for Antiangiogenesis Drugs
    John Fruehauf; Fiscal Year: 2002
    ..The total global market size for anti-angiogenesis drugs in cancer could reach $ 3 billion by 2005...
  64. PROTEIN ARGININE METHYLATION--STRUCTURES AND FUNCTIONS
    Xiaodong Cheng; Fiscal Year: 2004
    ..The potential catalytic and sequence recognition regions of PRMT will be confirmed by mutational analysis. ..