2 DNA Methylation and Histone Modifications in Patients With Cancer Potential Prognostic and Therapeutic Targets

Epigenetics, a combination of DNA modifications, chromatin organization, and variations in its associated proteins, configure a new entity that regulates gene expression throughout methylation, acetylation, and chromatin remodeling. In addition to silencing as a result of mutations, loss of heterozygosity, or classical genetic events epigenetic modification symbolizes essential early events during carcinogenesis and tumor development. The reversion of these epigenetic processes restoring normal expression of tumor-suppressor genes has consequently become a new therapeutic target in cancer treatment. Aberrant patterns of epigenetic modifications will be, in a near future, crucial parameters in cancer diagnosis and prognosis.

[1]  J. Davie,et al.  Histone modifications as a platform for cancer therapy , 2005, Journal of cellular biochemistry.

[2]  A. Ho,et al.  Role of histone deacetylase inhibitors in the treatment of cancer (Review). , 2004, International journal of oncology.

[3]  J. Loeffler,et al.  Targeting CREB-binding protein (CBP) loss of function as a therapeutic strategy in neurological disorders. , 2004, Biochemical pharmacology.

[4]  Paul Tempst,et al.  Histone Deimination Antagonizes Arginine Methylation , 2004, Cell.

[5]  W. Gerald,et al.  Clustering of gene hypermethylation associated with clinical risk groups in neuroblastoma. , 2004, Journal of the National Cancer Institute.

[6]  Gangning Liang,et al.  Preferential response of cancer cells to zebularine. , 2004, Cancer cell.

[7]  C. Peterson,et al.  Histones and histone modifications , 2004, Current Biology.

[8]  K. Bonham,et al.  Histone deacetylase inhibitors regulate p21WAF1 gene expression at the post‐transcriptional level in HepG2 cells , 2004, FEBS letters.

[9]  Yusuke Nakamura,et al.  SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells , 2004, Nature Cell Biology.

[10]  Yi Zhang,et al.  SUZ12 is required for both the histone methyltransferase activity and the silencing function of the EED-EZH2 complex. , 2004, Molecular cell.

[11]  S. Ait-Si-Ali,et al.  Chromatin dynamics and cancer , 2004, Cancer biology & therapy.

[12]  Charles Kooperberg,et al.  The histone modification pattern of active genes revealed through genome-wide chromatin analysis of a higher eukaryote. , 2004, Genes & development.

[13]  E. Wang,et al.  SRC Proximal and Core Promoter Elements Dictate TAF1 Dependence and Transcriptional Repression by Histone Deacetylase Inhibitors , 2004, Molecular and Cellular Biology.

[14]  C. Allis,et al.  Linking the epigenetic ‘language’ of covalent histone modifications to cancer , 2004, British Journal of Cancer.

[15]  J. Workman,et al.  Histone H3 variants and modifications on transcribed genes. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[16]  P. Atadja,et al.  Selective Growth Inhibition of Tumor Cells by a Novel Histone Deacetylase Inhibitor, NVP-LAQ824 , 2004, Cancer Research.

[17]  J. Herman,et al.  Generating mutations but providing chemosensitivity: the role of O6-methylguanine DNA methyltransferase in human cancer , 2004, Oncogene.

[18]  R. Eisenman,et al.  Histone sumoylation is associated with transcriptional repression , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[19]  P. Atadja,et al.  N-hydroxy-3-phenyl-2-propenamides as novel inhibitors of human histone deacetylase with in vivo antitumor activity: discovery of (2E)-N-hydroxy-3-[4-[[(2-hydroxyethyl)[2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide (NVP-LAQ824). , 2003, Journal of medicinal chemistry.

[20]  M. Paz,et al.  Genetic unmasking of epigenetically silenced tumor suppressor genes in colon cancer cells deficient in DNA methyltransferases. , 2003, Human molecular genetics.

[21]  Manel Esteller,et al.  Procaine is a DNA-demethylating agent with growth-inhibitory effects in human cancer cells. , 2003, Cancer research.

[22]  P. Finn,et al.  Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101. , 2003, Molecular cancer therapeutics.

[23]  C. Allis,et al.  Modulation of histone acetylation by [4-(acetylamino)-N-(2-amino-phenyl) benzamide] in HCT-8 colon carcinoma. , 2003, Molecular cancer therapeutics.

[24]  A. V. van Kuilenburg,et al.  Histone deacetylases (HDACs): characterization of the classical HDAC family. , 2003, The Biochemical journal.

[25]  Wei Ye,et al.  Inhibition of DNA methylation and reactivation of silenced genes by zebularine. , 2003, Journal of the National Cancer Institute.

[26]  J. Herman,et al.  A systematic profile of DNA methylation in human cancer cell lines. , 2003, Cancer research.

[27]  Manel Esteller,et al.  DNA demethylating agents and chromatin-remodelling drugs: which, how and why? , 2003, Current drug metabolism.

[28]  T. Ohno,et al.  Apicidin, a histone deacetylase inhibitor, induces differentiation of HL-60 cells. , 2003, Cancer letters.

[29]  J. Issa,et al.  Critical Role of Histone Methylation in Tumor Suppressor Gene Silencing in Colorectal Cancer , 2003, Molecular and Cellular Biology.

[30]  J. Herman,et al.  Dependence of histone modifications and gene expression on DNA hypermethylation in cancer. , 2002, Cancer research.

[31]  F. Sato,et al.  Pharmacologic unmasking of epigenetically silenced tumor suppressor genes in esophageal squamous cell carcinoma. , 2002, Cancer cell.

[32]  Peter A. Jones,et al.  Histone H3-lysine 9 methylation is associated with aberrant gene silencing in cancer cells and is rapidly reversed by 5-aza-2'-deoxycytidine. , 2002, Cancer research.

[33]  Manel Esteller,et al.  Hypermethylation-associated Inactivation of the Cellular Retinol-Binding-Protein 1 Gene in Human Cancer. , 2002, Cancer research.

[34]  Peter A. Jones,et al.  Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-Aza-2'-deoxycytidine (decitabine) treatment. , 2002, Blood.

[35]  A. Kimchi,et al.  Progress in differentiation induction as a treatment for acute promyelocytic leukemia and beyond. , 2002, Cancer research.

[36]  B. Turner,et al.  An increasingly complex code. , 2002, The Journal of clinical investigation.

[37]  Manel Esteller,et al.  DNA methylation: a profile of methods and applications. , 2002, BioTechniques.

[38]  H. Scher,et al.  The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[39]  M. Esteller.  CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future , 2002, Oncogene.

[40]  J. Christman,et al.  5-Azacytidine and 5-aza-2′-deoxycytidine as inhibitors of DNA methylation: mechanistic studies and their implications for cancer therapy , 2002, Oncogene.

[41]  A. Kalita,et al.  Sulfonamide anilides, a novel class of histone deacetylase inhibitors, are antiproliferative against human tumors. , 2002, Cancer research.

[42]  M. Szyf,et al.  The Oncoprotein Set/TAF-1β, an Inhibitor of Histone Acetyltransferase, Inhibits Active Demethylation of DNA, Integrating DNA Methylation and Transcriptional Silencing* , 2002, The Journal of Biological Chemistry.

[43]  C. Britten,et al.  A phase I study of pivaloyloxymethyl butyrate, a prodrug of the differentiating agent butyric acid, in patients with advanced solid malignancies. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[44]  Esteban Ballestar,et al.  The impact of chromatin in human cancer: linking DNA methylation to gene silencing. , 2002, Carcinogenesis.

[45]  Peter A. Jones,et al.  The fundamental role of epigenetic events in cancer , 2002, Nature Reviews Genetics.

[46]  Xiao-Fan Wang,et al.  HDAC6 is a microtubule-associated deacetylase , 2002, Nature.

[47]  J. Holland,et al.  Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[48]  Y. Yatabe,et al.  Aberrant hypermethylation of the CHFR prophase checkpoint gene in human lung cancers , 2002, Oncogene.

[49]  M. Grever,et al.  Impact of prolonged infusions of the putative differentiating agent sodium phenylbutyrate on myelodysplastic syndromes and acute myeloid leukemia. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[50]  Ricky W. Johnstone,et al.  Histone-deacetylase inhibitors: novel drugs for the treatment of cancer , 2002, Nature Reviews Drug Discovery.

[51]  S. Goodman,et al.  Hypermethylation of the DNA repair gene O(6)-methylguanine DNA methyltransferase and survival of patients with diffuse large B-cell lymphoma. , 2002, Journal of the National Cancer Institute.

[52]  Ping Zhu,et al.  Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells , 2001, The EMBO journal.

[53]  J. Herman,et al.  DNA methylation patterns in hereditary human cancers mimic sporadic tumorigenesis. , 2001, Human molecular genetics.

[54]  S. Piantadosi,et al.  Reversal of GSTP1 CpG island hypermethylation and reactivation of pi-class glutathione S-transferase (GSTP1) expression in human prostate cancer cells by treatment with procainamide. , 2001, Cancer research.

[55]  P. Marks,et al.  Histone deacetylases and cancer: causes and therapies , 2001, Nature Reviews Cancer.

[56]  M. Szyf,et al.  Demethylase Activity Is Directed by Histone Acetylation* , 2001, The Journal of Biological Chemistry.

[57]  M. Guenther,et al.  Histone Deacetylase Is a Direct Target of Valproic Acid, a Potent Anticonvulsant, Mood Stabilizer, and Teratogen* , 2001, The Journal of Biological Chemistry.

[58]  J. Herman,et al.  Molecular detection of prostate cancer in urine by GSTP1 hypermethylation. , 2001, Clinical cancer research : an official journal of the American Association for Cancer Research.

[59]  C. Pickart,et al.  Ubiquitin enters the new millennium. , 2001, Molecular cell.

[60]  J. Herman,et al.  Promoter hypermethylation of the DNA repair gene O(6)-methylguanine-DNA methyltransferase is associated with the presence of G:C to A:T transition mutations in p53 in human colorectal tumorigenesis. , 2001, Cancer research.

[61]  J. Herman,et al.  Promoter hypermethylation--can this change alone ever designate true tumor suppressor gene function? , 2001, Journal of the National Cancer Institute.

[62]  Christopher B Umbricht,et al.  Detection of breast cancer cells in ductal lavage fluid by methylation-specific PCR , 2001, The Lancet.

[63]  J. Herman,et al.  A gene hypermethylation profile of human cancer. , 2001, Cancer research.

[64]  K. Struhl,et al.  Histone Acetylation at Promoters Is Differentially Affected by Specific Activators and Repressors , 2001, Molecular and Cellular Biology.

[65]  J. Herman,et al.  p14ARF silencing by promoter hypermethylation mediates abnormal intracellular localization of MDM2. , 2001, Cancer research.

[66]  S. Croft,et al.  The synthesis of cyclic tetrapeptoid analogues of the antiprotozoal natural product apicidin. , 2001, Bioorganic & medicinal chemistry letters.

[67]  J. Jen,et al.  Promoter hypermethylation patterns of p16, O6-methylguanine-DNA-methyltransferase, and death-associated protein kinase in tumors and saliva of head and neck cancer patients. , 2001, Cancer research.

[68]  J. Lutterbaugh,et al.  Detection of aberrantly methylated hMLH1 promoter DNA in the serum of patients with microsatellite unstable colon cancer. , 2001, Cancer research.

[69]  J. Minna,et al.  Promoter methylation and silencing of the retinoic acid receptor-beta gene in lung carcinomas. , 2001, Journal of the National Cancer Institute.

[70]  M. Yoshida,et al.  Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[71]  M. Müller,et al.  Methylation-specific PCR (MSP) for detection of tumour DNA in the blood plasma and serum of patients with prostate cancer , 2000, Prostate Cancer and Prostatic Diseases.

[72]  S. Groshen,et al.  Hypermethylated APC DNA in plasma and prognosis of patients with esophageal adenocarcinoma. , 2000, Journal of the National Cancer Institute.

[73]  Scar,et al.  Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. , 2000, The New England journal of medicine.

[74]  J. Sludden,et al.  Reversal of drug resistance in human tumor xenografts by 2'-deoxy-5-azacytidine-induced demethylation of the hMLH1 gene promoter. , 2000, Cancer research.

[75]  J. Herman,et al.  Predicting lung cancer by detecting aberrant promoter methylation in sputum. , 2000, Cancer research.

[76]  T. Bestor,et al.  The DNA methyltransferases of mammals. , 2000, Human molecular genetics.

[77]  J. Weniger,et al.  Histone deacetylase inhibitors and cell proliferation in pea root meristems. , 2000, Phytochemistry.

[78]  J. Herman,et al.  Analysis of adenomatous polyposis coli promoter hypermethylation in human cancer. , 2000, Cancer research.

[79]  J. Herman,et al.  Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is associated with G to A mutations in K-ras in colorectal tumorigenesis. , 2000, Cancer research.

[80]  K D Robertson,et al.  DNA methylation: past, present and future directions. , 2000, Carcinogenesis.

[81]  C. Allis,et al.  The language of covalent histone modifications , 2000, Nature.

[82]  C. Allis,et al.  Methylation of histone H3 at lysine 4 is highly conserved and correlates with transcriptionally active nuclei in Tetrahymena. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[83]  A. Bird,et al.  Methylation-Induced Repression— Belts, Braces, and Chromatin , 1999, Cell.

[84]  Paul Tempst,et al.  MBD2 is a transcriptional repressor belonging to the MeCP1 histone deacetylase complex , 1999, Nature Genetics.

[85]  J. Herman,et al.  Molecular detection of neoplastic cells in lymph nodes of metastatic colorectal cancer patients predicts recurrence. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[86]  E. Ballestar,et al.  Mi-2 complex couples DNA methylation to chromatin remodelling and histone deacetylation , 1999, Nature Genetics.

[87]  J. Herman,et al.  Transcriptional silencing of the p73 gene in acute lymphoblastic leukemia and Burkitt's lymphoma is associated with 5' CpG island methylation. , 1999, Cancer research.

[88]  Fred Winston,et al.  The bromodomain: a chromatin-targeting module? , 1999, Nature Structural Biology.

[89]  Lei Zeng,et al.  Structure and ligand of a histone acetyltransferase bromodomain , 1999, Nature.

[90]  T. Tsuruo,et al.  A synthetic inhibitor of histone deacetylase, MS-27-275, with marked in vivo antitumor activity against human tumors. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[91]  J. Herman,et al.  Hypermethylation of the hMLH1 gene promoter in human gastric cancers with microsatellite instability. , 1999, Cancer research.

[92]  J. Herman,et al.  Molecular detection of tumor cells in bronchoalveolar lavage fluid from patients with early stage lung cancer. , 1999, Journal of the National Cancer Institute.

[93]  J. Herman,et al.  Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. , 1999, Cancer research.

[94]  Manel Esteller,et al.  MLH1 promoter hypermethylation is associated with the microsatellite instability phenotype in sporadic endometrial carcinomas , 1998, Oncogene.

[95]  Peter A. Jones,et al.  The Human ARF Cell Cycle Regulatory Gene Promoter Is a CpG Island Which Can Be Silenced by DNA Methylation and Down-Regulated by Wild-Type p53 , 1998, Molecular and Cellular Biology.

[96]  Rudolf Jaenisch,et al.  DNA hypomethylation leads to elevated mutation rates , 1998, Nature.

[97]  A. Razin,et al.  CpG methylation, chromatin structure and gene silencing—a three‐way connection , 1998, The EMBO journal.

[98]  J. Herman,et al.  Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[99]  J. Herman,et al.  Hypermethylation can selectively silence individual p16ink4A alleles in neoplasia. , 1998, Cancer research.

[100]  M. Newton,et al.  Overcoming cellular senescence in human cancer pathogenesis. , 1998, Genes & development.

[101]  T. Richmond,et al.  Crystal structure of the nucleosome core particle at 2.8 Å resolution , 1997, Nature.

[102]  T. Bestor,et al.  DNA (cytosine-5)-methyltransferases in mouse cells and tissues. Studies with a mechanism-based probe. , 1997, Journal of molecular biology.

[103]  G. Schwartsmann,et al.  Decitabine (5-Aza-2'-deoxycytidine; DAC) plus daunorubicin as a first line treatment in patients with acute myeloid leukemia: preliminary observations. , 1997, Leukemia.

[104]  M. Loda,et al.  Methylation of the hMLH1 promoter correlates with lack of expression of hMLH1 in sporadic colon tumors and mismatch repair-defective human tumor cell lines. , 1997, Cancer research.

[105]  R. Momparler,et al.  Activation of the retinoic acid receptor β gene by 5-aza-2’-deoxycytidine in human DLD-1 colon carcinoma cells , 1997, Anti-cancer drugs.

[106]  D M Schmatz,et al.  Apicidin: a novel antiprotozoal agent that inhibits parasite histone deacetylase. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[107]  J. Herman,et al.  Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[108]  V. Chapman,et al.  Identification of Grf1 on mouse chromosome 9 as an imprinted gene by RLGS–M , 1996, Nature Genetics.

[109]  J. Herman,et al.  Hypermethylation-associated inactivation indicates a tumor suppressor role for p15INK4B. , 1996, Cancer research.

[110]  J. Herman,et al.  Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. , 1995, Cancer research.

[111]  R. Beart,et al.  Methylation of the 5' CpG island of the p16/CDKN2 tumor suppressor gene in normal and transformed human tissues correlates with gene silencing. , 1995, Cancer research.

[112]  J. Herman,et al.  5′ CpG island methylation is associated with transcriptional silencing of the tumour suppressor p16/CDKN2/MTS1 in human cancers , 1995, Nature Medicine.

[113]  M. Lea,et al.  Discordant effects of butyrate analogues on erythroleukemia cell proliferation, differentiation and histone deacetylase. , 1995, Anticancer research.

[114]  S. Baylin,et al.  Methylation of the estrogen receptor gene CpG island marks loss of estrogen receptor expression in human breast cancer cells. , 1994, Cancer research.

[115]  A. Bird,et al.  Number of CpG islands and genes in human and mouse. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[116]  C. Schiffer,et al.  Effects of treatment with 5-azacytidine on the in vivo and in vitro hematopoiesis in patients with myelodysplastic syndromes. , 1993, Leukemia.

[117]  Minoru Yoshida,et al.  [Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A]. , 1990, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[118]  B. Vogelstein,et al.  A genetic model for colorectal tumorigenesis , 1990, Cell.

[119]  S. Monfardini,et al.  5-Aza-2'-deoxycytidine as a differentiation inducer in acute myeloid leukaemias and myelodysplastic syndromes of the elderly. , 1989, Bone marrow transplantation.

[120]  B. Horsthemke,et al.  Epigenetic changes may contribute to the formation and spontaneous regression of retinoblastoma , 1989, Human Genetics.

[121]  R. Chalkley,et al.  The effect of sodium butyrate on histone modification , 1978, Cell.

[122]  David Horn,et al.  Histone deacetylases. , 2008, Advances in experimental medicine and biology.

[123]  J. Davie,et al.  Histone modifications in corepressor functions. , 2004, Current topics in developmental biology.

[124]  Andrew J. Bannister,et al.  Histone methylation: recognizing the methyl mark. , 2004, Methods in enzymology.

[125]  Matty P. Weijenberg,et al.  A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer , 2002, Nature Genetics.

[126]  J. Sudbø,et al.  Gene-expression profiles in hereditary breast cancer. , 2001, The New England journal of medicine.

[127]  J. Herman,et al.  Hypermethylation-associated inactivation of p14(ARF) is independent of p16(INK4a) methylation and p53 mutational status. , 2000, Cancer research.

[128]  J. Herman,et al.  Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer , 1999, Nature Genetics.

[129]  J. Herman,et al.  Detection of aberrant promoter hypermethylation of tumor suppressor genes in serum DNA from non-small cell lung cancer patients. , 1999, Cancer research.

[130]  P. Néve,et al.  Continuous infusion of low-dose 5-Aza-2′-deoxycytidine in elderly patients with high-risk myelodysplastic syndrome , 1997, Leukemia.