title: Epigenetic aberrations and therapeutic implications in gliomas.
abstract: Almost all cancer cells have multiple epigenetic abnormalities, which combine with genetic changes to affect many cellular processes, including cell proliferation and invasion, by silencing tumor-suppressor genes. In this review, we focus on the epigenetic mechanisms of DNA hypomethylation and CpG island hypermethylation in gliomas. Aberrant hypermethylation in promoter CpG islands has been recognized as a key mechanism involved in the silencing of cancer-associated genes and occurs at genes with diverse functions related to tumorigenesis and tumor progression. Such promoter hypermethylation can modulate the sensitivity of glioblastomas to drugs and radiotherapy. As an example, the methylation of the O6-methylguanine DNA methyltransferase (MGMT) promoter is a specific predictive biomarker of tumor responsiveness to chemotherapy with alkylating agents. Further, we reviewed reports on pyrosequencing - a simple technique for the accurate and quantitative analysis of DNA methylation. We believe that the quantification of MGMT methylation by pyrosequencing might enable the selection of patients who are most likely to benefit from chemotherapy. Finally, we also evaluated the potential of de novo NY-ESO-1, the most immunogenic cancer/testis antigen (CTA) discovered thus far, as an immunotherapy target. The use of potent epigenetics-based therapy for cancer cells might restore the abnormally regulated epigenomes to a more normal state through epigenetic reprogramming. Thus, epigenetic therapy may be a promising and potent treatment for human neoplasia.
authors.affiliation: Department of Neurosurgery, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Natsume
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kondo
authors.forename: Motokazu
authors.initials: M
authors.lastname: Ito
authors.forename: Kazuya
authors.initials: K
authors.lastname: Motomura
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Wakabayashi
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshida
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics* / Q000628:therapy; D018899:CpG Islands; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D044127:Epigenesis, Genetic; D005910:Glioma / Q000235:genetics* / Q000628:therapy; D006801:Humans; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
references.citation: PLoS Genet. 2007 Sep;3(9):1709-23
references.pmid: 17892325
references.citation: N Engl J Med. 2005 Mar 10;352(10):997-1003
references.pmid: 15758010
references.citation: Semin Cancer Biol. 1999 Oct;9(5):329-37
references.pmid: 10547341
references.citation: Proc Natl Acad Sci U S A. 1997 Mar 4;94(5):1914-8
references.pmid: 9050879
references.citation: Cancer Metastasis Rev. 2004 Jan-Jun;23(1-2):29-39
references.pmid: 15000147
references.citation: Cell. 2007 Feb 23;128(4):683-92
references.pmid: 17320506
references.citation: Science. 2003 Apr 18;300(5618):455
references.pmid: 12702868
references.citation: Nat Rev Drug Discov. 2006 Jan;5(1):37-50
references.pmid: 16485345
references.citation: Cell. 1979 Aug;17(4):771-9
references.pmid: 90553
references.citation: Ann Neurol. 1988 Apr;23(4):360-4
references.pmid: 3382171
references.citation: Cancer Res. 1998 Mar 1;58(5):1068-73
references.pmid: 9500473
references.citation: Nat Genet. 2002 Jun;31(2):141-9
references.pmid: 11992124
references.citation: Nat Rev Genet. 2002 Jun;3(6):415-28
references.pmid: 12042769
references.citation: Cancer Res. 1999 Feb 15;59(4):793-7
references.pmid: 10029064
references.citation: Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4760-5
references.pmid: 10781081
references.citation: Science. 2005 Mar 25;307(5717):1976-8
references.pmid: 15731405
references.citation: J Clin Oncol. 2006 Jun 20;24(18):2707-14
references.pmid: 16782910
references.citation: BMC Cancer. 2004 Sep 14;4:65
references.pmid: 15367334
references.citation: Electrophoresis. 2002 Dec;23(24):4072-9
references.pmid: 12481262
references.citation: Biotechniques. 2003 Jul;35(1):152-6
references.pmid: 12866415
references.citation: Annu Rev Immunol. 1994;12:337-65
references.pmid: 8011285
references.citation: Nature. 1980 Dec 25;288(5792):724-7
references.pmid: 6256643
references.citation: Cancer. 1993 Apr 15;71(8):2585-97
references.pmid: 8453582
references.citation: Mol Endocrinol. 2005 Mar;19(3):563-73
references.pmid: 15677708
references.citation: Int J Cancer. 2008 Jun 1;122(11):2542-53
references.pmid: 18240144
references.citation: Anal Biochem. 2004 Oct 1;333(1):119-27
references.pmid: 15351288
references.citation: Nat Genet. 1999 Feb;21(2):163-7
references.pmid: 9988266
references.citation: Trends Genet. 2000 Apr;16(4):168-74
references.pmid: 10729832
references.citation: Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9821-6
references.pmid: 8790415
references.citation: Nat Genet. 1999 Jan;21(1):103-7
references.pmid: 9916800
references.citation: Curr Opin Oncol. 2003 Nov;15(6):446-51
references.pmid: 14624227
references.citation: J Mol Diagn. 2007 Jul;9(3):368-81
references.pmid: 17591937
references.citation: Cancer Chemother Pharmacol. 2008 Apr;61(4):653-9
references.pmid: 17564708
references.citation: Cancer Genet Cytogenet. 2006 Jan 15;164(2):172-3
references.pmid: 16434325
references.citation: Cancer Res. 1996 May 15;56(10):2405-10
references.pmid: 8625319
references.citation: Biotechniques. 2003 Jul;35(1):146-50
references.pmid: 12866414
references.citation: Cancer Res. 2002 Nov 15;62(22):6456-61
references.pmid: 12438235
references.citation: Cell Oncol. 2004;26(5-6):291-9
references.pmid: 15623939
references.citation: Ann Neurol. 2006 Dec;60(6):740-3
references.pmid: 17192931
references.citation: Cancer Res. 1993 Jul 15;53(14):3416-20
references.pmid: 8324751
references.citation: Biotechniques. 2006 Jun;40(6):721-2, 724, 726
references.pmid: 16774114
references.citation: Cancer Res. 2005 Apr 1;65(7):2565-71
references.pmid: 15805250
references.citation: Carcinogenesis. 2003 Apr;24(4):625-35
references.pmid: 12727789
references.citation: Cancer Res. 2006 Sep 1;66(17):8469-76
references.pmid: 16951158
references.citation: J Neurooncol. 2009 Mar;92(1):15-22
references.pmid: 19030781
references.citation: Acta Neuropathol. 2005 Aug;110(2):178-84
references.pmid: 16025287
references.citation: Cancer Res. 1996 Dec 1;56(23):5356-9
references.pmid: 8968084
references.citation: Curr Opin Genet Dev. 1995 Jun;5(3):309-14
references.pmid: 7549424
references.citation: Genet Anal Tech Appl. 1992 Apr;9(2):48-53
references.pmid: 1356381
references.citation: Clin Cancer Res. 2007 Apr 15;13(8):2344-53
references.pmid: 17438093
references.citation: Clin Cancer Res. 2009 Jun 15;15(12):3938-46
references.pmid: 19509174
references.citation: Nat Genet. 2008 Jun;40(6):741-50
references.pmid: 18488029
references.citation: Oncogene. 2008 Jan 10;27(3):358-65
references.pmid: 17653095
references.citation: J Clin Oncol. 2006 Jun 20;24(18):2715-22
references.pmid: 16782911
references.citation: Science. 1998 Jul 17;281(5375):363, 365
references.pmid: 9705713
references.citation: Cancer Res. 2000 Mar 15;60(6):1654-62
references.pmid: 10749136
references.citation: Cancer Res. 2005 Sep 1;65(17):7573-9
references.pmid: 16140920
references.citation: Acta Neuropathol. 2003 Nov;106(5):479-85
references.pmid: 12904991
references.citation: Nature. 2002 Sep 26;419(6905):407-11
references.pmid: 12353038
references.citation: Nature. 2008 Jul 3;454(7200):49-55
references.pmid: 18509334
references.citation: Genes Dev. 2004 Jul 1;18(13):1592-605
references.pmid: 15231737
references.citation: Science. 2007 Nov 16;318(5853):1108-13
references.pmid: 17932254
references.citation: Nucleic Acids Res. 1983 Oct 11;11(19):6883-94
references.pmid: 6314264
references.citation: Lab Invest. 2001 Jan;81(1):77-82
references.pmid: 11204276