[DNA methylation. From basic research to routine diagnostics].
On a molecular level cancer is characterized not only by genetic defects, such as deletions, mutations or translocations, but also by epigenetic lesions. The most important epigenetic mechanisms are DNA methylation, Polycomb/trithorax complexes, histon modifications, non-coding RNAs, and chromosomal territories. These epigenetic mechanisms contribute to a stable modification of gene expression without changes in primary DNA sequence. During the development and progression of human tumours a gene-specific hypermethylation with resulting repression of transcription can occur. At the same time, global hypomethylation can very often be observed which contributes to an increase in chromosomal instability. In tumour pathology, the detection of somatic hMLH1 hypermethylation is important for molecular diagnostics of Lynch syndrome. The detection of MGMT gene methylation is a good prognostic and predictive factor for glioblastoma patients. Performing DNA methylation assays for routine diagnostics requires technical as well as theoretical expertise.
Lehmann
U
U
Institut für Pathologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover. Lehmann.Ulrich@MH-Hannover.de
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D043171:Chromosomal Instability; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D025202:Molecular Diagnostic Techniques; D000070957:MutL Protein Homolog 1; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D000070957:MutL Protein Homolog 1; D045643:DNA Repair Enzymes
Nat Rev Cancer. 2004 Dec;4(12):988-93
15573120
Cancer Cell. 2010 Jan 19;17(1):13-27
20060365
Science. 2009 May 15;324(5929):929-30
19372393
Cancer Lett. 2008 Sep 18;268(2):177-86
18471961
Nucleic Acids Res. 2001 Jul 1;29(13):E65-5
11433041
Epigenomics. 2009 Dec;1(2):239-59
20495664
Pediatr Blood Cancer. 2007 Apr;48(4):403-7
16609952
Genes Dev. 2006 Dec 1;20(23):3215-31
17158741
J Med Genet. 2009 Dec;46(12):793-802
19564652
Science. 1998 Jul 17;281(5375):363, 365
9705713
Biotechniques. 2002 Sep;33(3):632, 634, 636-49
12238773
Trends Mol Med. 2009 Mar;15(3):120-8
19246245
Cell. 2007 Feb 23;128(4):693-705
17320507
Curr Opin Cell Biol. 2006 Jun;18(3):307-16
16687245
J Pathol. 2008 Jan;214(1):10-6
17973250
Am J Pathol. 2009 Oct;175(4):1353-61
19717641
Nat Rev Genet. 2010 Mar;11(3):191-203
20125086
Clin Cancer Res. 2009 Jun 15;15(12):3927-37
19509173
Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1827-31
1542678
N Engl J Med. 2005 Mar 10;352(10):997-1003
15758010
Histol Histopathol. 2009 Apr;24(4):511-8
19224454
Oncogene. 2007 Nov 29;26(54):7596-600
17546041
Trends Biochem Sci. 2006 Feb;31(2):89-97
16403636
Nat Clin Pract Oncol. 2005 Dec;2 Suppl 1:S4-11
16341240
Gynecol Oncol. 2009 Feb;112(2):293-9
19054549
Nature. 1983 Jan 6;301(5895):89-92
6185846
J Cell Sci. 2009 Aug 15;122(Pt 16):2787-91
19657014
Curr Opin Cell Biol. 2007 Jun;19(3):290-7
17481880
Nat Rev Cancer. 2003 Apr;3(4):253-66
12671664
J Clin Oncol. 2009 Dec 1;27(34):5743-50
19805672
Science. 2009 May 15;324(5929):930-5
19372391
J Pathol. 2010 Jan;220(2):126-39
19882673
Gastroenterology. 2010 Jun;138(6):2073-2087.e3
20420947
Clin Cancer Res. 2009 Nov 1;15(21):6683-93
19861461
BMC Med Genomics. 2009 May 27;2:30
19473516
Epigenetics. 2006 Apr-Jun;1(2):76-80
17998809
Nature. 2007 May 24;447(7143):396-8
17522671
Virology. 2009 Jun 20;389(1-2):100-7
19443004
Blood. 1987 Aug;70(2):412-7
3607279
Nat Rev Cancer. 2005 Mar;5(3):223-31
15719030
Adv Genet. 2008;61:225-46
18282508
J Mol Med (Berl). 2006 May;84(5):365-77
16416310
Am J Med Genet A. 2008 Aug 15;146A(16):2041-52
18627066
Hum Genet. 1989 Sep;83(2):155-8
2550354
J Clin Oncol. 2004 Nov 15;22(22):4632-42
15542813
Leukemia. 2008 Oct;22(10):1954-6
18385753
J Pathol. 2001 Sep;195(1):97-110
11568896
Oncogene. 2002 Aug 12;21(35):5361-79
12154399
Cancer Res. 2010 Apr 15;70(8):3098-108
20388775
Nat Genet. 2009 Jan;41(1):112-7
19098912
Eur J Obstet Gynecol Reprod Biol. 2009 Dec;147(2):215-20
19819061
Int J Gynecol Cancer. 2009 Apr;19(3):321-5
19407553