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DNA methylation profiling in cancer

Published online by Cambridge University Press:  28 July 2010

Yutaka Kondo  and
Jean-Pierre J. Issa
Yutaka Kondo*
Affiliation:
Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
Jean-Pierre J. Issa
Affiliation:
Department of Leukemia, M. D. Anderson Cancer Center, University of Texas, Houston, TX 77030, USA.
*
*Corresponding author: Yutaka Kondo, Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. E-mail: [email protected]
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Abstract

Aberrant DNA methylation in the genome is found in almost all types of cancer and contributes to malignant transformation by silencing multiple tumour-suppressor genes, sometimes simultaneously. Therefore, deciphering the signature of DNA methylation in each tumour is required to better understand tumour behaviour and might be of benefit for clinical diagnostics and therapy. Recent technologies for high-throughput genome-wide DNA methylation analyses are promising and potent tools for epigenetic profiling. Since epigenetic therapy is now in clinical use or trials for several types of cancers, efficient epigenetic profiling is required. In this review, the current key technologies available to assess genome-wide DNA methylation are introduced and the implications of DNA methylation profiling in human cancers are discussed.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 12 , January 2010 , e23
Copyright
Copyright © Cambridge University Press 2010

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References

References

1Ramsahoye, B.H. et al. (2000) Non-CpG methylation is prevalent in embryonic stem cells and may be mediated by DNA methyltransferase 3a. Proceedings of the National Academy of Sciences of the United States of America 97, 5237-5242Google Scholar
2Lister, R. et al. (2009) Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462, 315-322CrossRefGoogle ScholarPubMed
3Bestor, T.H. et al. (1992) CpG islands in mammalian gene promoters are inherently resistant to de novo methylation. Genetic Analysis, Techniques and Applications 9, 48-53Google Scholar
4Cross, S.H. and Bird, A.P. (1995) CpG islands and genes. Current Opinion in Genetics and Development 5, 309-314CrossRefGoogle ScholarPubMed
5Illingworth, R. et al. (2008) A novel CpG island set identifies tissue-specific methylation at developmental gene loci. PLoS Biology 6, e22CrossRefGoogle ScholarPubMed
6Bird, A. (2002) DNA methylation patterns and epigenetic memory. Genes and Development 16, 6-21Google Scholar
7Jones, P.A. and Laird, P.W. (1999) Cancer epigenetics comes of age. Nature Genetics 21, 163-167CrossRefGoogle ScholarPubMed
8Jones, P.A. and Baylin, S.B. (2007) The epigenomics of cancer. Cell 128, 683-692CrossRefGoogle ScholarPubMed
9Issa, J.P. (2005) Optimizing therapy with methylation inhibitors in myelodysplastic syndromes: dose, duration, and patient selection. Nature Clinical Practice Oncology 2 Suppl. 1, S24-29Google Scholar
10Shen, L. et al. (2010) DNA methylation predicts survival and response to therapy in patients with myelodysplastic syndromes. Journal of Clinical Oncology 28, 605-613Google Scholar
11Yoo, C.B. and Jones, P.A. (2006) Epigenetic therapy of cancer: past, present and future. Nature Reviews Drug Discovery 5, 37-50Google Scholar
12Marks, P.A. and Xu, W.S. (2009) Histone deacetylase inhibitors: Potential in cancer therapy. Journal of Cellular Biochemistry 107, 600-608CrossRefGoogle ScholarPubMed
13Beck, S. and Rakyan, V.K. (2008) The methylome: approaches for global DNA methylation profiling. Trends in Genetics 24, 231-237CrossRefGoogle ScholarPubMed
14Laird, P.W. (2010) Principles and challenges of genome-wide DNA methylation analysis. Nature Reviews Genetics 11, 191-203Google Scholar
15Hayashizaki, Y. et al. (1993) Restriction landmark genomic scanning method and its various applications. Electrophoresis 14, 251-258Google Scholar
16Kawai, J. et al. (1993) Methylation profiles of genomic DNA of mouse developmental brain detected by restriction landmark genomic scanning (RLGS) method. Nucleic Acids Research 21, 5604-5608CrossRefGoogle ScholarPubMed
17Okano, M. et al. (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99, 247-257CrossRefGoogle Scholar
18Eden, A. et al. (2003) Chromosomal instability and tumors promoted by DNA hypomethylation. Science 300, 455CrossRefGoogle ScholarPubMed
19Cadieux, B. et al. (2006) Genome-wide hypomethylation in human glioblastomas associated with specific copy number alteration, methylenetetrahydrofolate reductase allele status, and increased proliferation. Cancer Research 66, 8469-8476CrossRefGoogle ScholarPubMed
20De Smet, C. et al. (1999) DNA methylation is the primary silencing mechanism for a set of germ line- and tumor-specific genes with a CpG-rich promoter. Molecular and Cellular Biology 19, 7327-7335Google Scholar
21Sakatani, T. et al. (2005) Loss of imprinting of Igf2 alters intestinal maturation and tumorigenesis in mice. Science 307, 1976-1978CrossRefGoogle ScholarPubMed
22Baylin, S.B. et al. (1998) Alterations in DNA methylation: a fundamental aspect of neoplasia. Advances in Cancer Research 72, 141-196CrossRefGoogle ScholarPubMed
23Jones, P.A. and Baylin, S.B. (2002) The fundamental role of epigenetic events in cancer. Nature Reviews Genetics 3, 415-428CrossRefGoogle ScholarPubMed
24Ting, A.H., McGarvey, K.M. and Baylin, S.B. (2006) The cancer epigenome–components and functional correlates. Genes and Development 20, 3215-3231Google Scholar
25Kondo, Y. and Issa, J.P. (2004) Epigenetic changes in colorectal cancer. Cancer and Metastasis Reviews 23, 29-39CrossRefGoogle ScholarPubMed
26Keshet, I. et al. (2006) Evidence for an instructive mechanism of de novo methylation in cancer cells. Natue Genetics 38, 149-153CrossRefGoogle ScholarPubMed
27Feltus, F.A. et al. (2003) Predicting aberrant CpG island methylation. Proceedings of the National Academy of Sciences of the United States of America 100, 12253-12258Google Scholar
28Ohm, J.E. et al. (2007) A stem cell-like chromatin pattern may predispose tumor suppressor genes to DNA hypermethylation and heritable silencing. Nature Genetics 39, 237-242CrossRefGoogle ScholarPubMed
29Widschwendter, M. et al. (2007) Epigenetic stem cell signature in cancer. Nature Genetics 39, 157-158CrossRefGoogle ScholarPubMed
30Schlesinger, Y. et al. (2007) Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer. Nature Genetics 39, 232-236Google Scholar
31Kondo, Y. et al. (2008) Gene silencing in cancer by histone H3 lysine 27 trimethylation independent of promoter DNA methylation. Nature Genetics 40, 741-750Google Scholar
32Gal-Yam, E.N. et al. (2008) Frequent switching of Polycomb repressive marks and DNA hypermethylation in the PC3 prostate cancer cell line. Proceedings of the National Academy of Sciences of the United States of America 105, 12979-12984Google Scholar
33Takeshima, H. et al. (2009) The presence of RNA polymerase II, active or stalled, predicts epigenetic fate of promoter CpG islands. Genome Research 19, 1974-1982Google Scholar
34Toyota, M. et al. (1999) CpG island methylator phenotype in colorectal cancer. Proceedings of the National Academy of Sciences of the United States of America 96, 8681-8686CrossRefGoogle ScholarPubMed
35Shen, L. et al. (2007) Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer. Proceedings of the National Academy of Sciences of the United States of America 104, 18654-18659CrossRefGoogle ScholarPubMed
36Ogino, S. et al. (2006) CpG island methylator phenotype-low (CIMP-low) in colorectal cancer: possible associations with male sex and KRAS mutations. Journal of Molecular Diagnostics 8, 582-588CrossRefGoogle ScholarPubMed
37Yagi, K. et al. Three DNA methylation epigenotypes in human colorectal cancer. Clinical Cancer Research 16, 21-33CrossRefGoogle Scholar
38Baylin, S.B. and Ohm, J.E. (2006) Epigenetic gene silencing in cancer – a mechanism for early oncogenic pathway addiction? Nature Reviews Cancer 6, 107-116CrossRefGoogle Scholar
39Issa, J.P. (2004) CpG island methylator phenotype in cancer. Nature Reviews Cancer 4, 988-993CrossRefGoogle ScholarPubMed
40Issa, J.P. (2008) Colon cancer: it's CIN or CIMP. Clinical Cancer Research 14, 5939-5940CrossRefGoogle ScholarPubMed
41Kanai, Y. et al. (2001) DNA methyltransferase expression and DNA methylation of CPG islands and peri-centromeric satellite regions in human colorectal and stomach cancers. International Journal of Cancer 91, 205-212Google Scholar
42An, B. et al. A characteristic methylation profile in CpG island methylator phenotype-negative distal colorectal cancers. International Journal of Cancer 2010 Feb 3. [Epub ahead of print]CrossRefGoogle Scholar
43Toyota, M. et al. (1999) Aberrant methylation in gastric cancer associated with the CpG island methylator phenotype. Cancer Research 59, 5438-5442Google Scholar
44Kim, H. et al. (2003) Concerted promoter hypermethylation of hMLH1, p16INK4A, and E-cadherin in gastric carcinomas with microsatellite instability. Journal of Pathology 200, 23-31Google Scholar
45Kusano, M. et al. (2006) Genetic, epigenetic, and clinicopathologic features of gastric carcinomas with the CpG island methylator phenotype and an association with Epstein-Barr virus. Cancer 106, 1467-1479Google Scholar
46Weber, M. et al. (2005) Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nature Genetics 37, 853-862Google Scholar
47Zhang, X. et al. (2006) Genome-wide high-resolution mapping and functional analysis of DNA methylation in arabidopsis. Cell 126, 1189-1201CrossRefGoogle ScholarPubMed
48Rauch, T. et al. (2006) MIRA-assisted microarray analysis, a new technology for the determination of DNA methylation patterns, identifies frequent methylation of homeodomain-containing genes in lung cancer cells. Cancer Research 66, 7939-7947CrossRefGoogle ScholarPubMed
49Khulan, B. et al. (2006) Comparative isoschizomer profiling of cytosine methylation: the HELP assay. Genome Research 16, 1046-1055Google Scholar
50Estecio, M.R. et al. (2007) High-throughput methylation profiling by MCA coupled to CpG island microarray. Genome Research 17, 1529-1536CrossRefGoogle ScholarPubMed
51Shen, L. et al. (2007) Genome-wide profiling of DNA methylation reveals a class of normally methylated CpG island promoters. PLoS Genetics 3, 2023-2036Google Scholar
52Gao, W. et al. (2008) Variable DNA methylation patterns associated with progression of disease in hepatocellular carcinomas. Carcinogenesis 29, 1901-1910CrossRefGoogle ScholarPubMed
53Omura, N. et al. (2008) Genome-wide profiling of methylated promoters in pancreatic adenocarcinoma. Cancer Biology and Therapy 7, 1146-1156Google Scholar
54Clark, S.J. et al. (1994) High sensitivity mapping of methylated cytosines. Nucleic Acids Research 22, 2990-2997Google Scholar
55Colella, S. et al. (2003) Sensitive and quantitative universal Pyrosequencing methylation analysis of CpG sites. Biotechniques 35, 146-150Google Scholar
56Xiong, Z. and Laird, P.W. (1997) COBRA: a sensitive and quantitative DNA methylation assay. Nucleic Acids Research 25, 2532-2534CrossRefGoogle Scholar
57Herman, J.G. et al. (1996) Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proceedings of the National Academy of Sciences of the United States of America 93, 9821-9826CrossRefGoogle ScholarPubMed
58Bibikova, M. et al. (2006) High-throughput DNA methylation profiling using universal bead arrays. Genome Research 16, 383-393Google Scholar
59Albert, T.J. et al. (2007) Direct selection of human genomic loci by microarray hybridization. Nature Methods 4, 903-905Google Scholar
60Meissner, A. et al. (2008) Genome-scale DNA methylation maps of pluripotent and differentiated cells. Nature 454, 766-770Google Scholar
61Hodges, E. et al. (2009) High definition profiling of mammalian DNA methylation by array capture and single molecule bisulfite sequencing. Genome Research 19, 1593-1605Google Scholar
62Li, J.B. et al. (2009) Multiplex padlock targeted sequencing reveals human hypermutable CpG variations. Genome Research 19, 1606-1615CrossRefGoogle ScholarPubMed
63Van Rijnsoever, M. et al. (2003) CpG island methylator phenotype is an independent predictor of survival benefit from 5-fluorouracil in stage III colorectal cancer. Clinical Cancer Research 9, 2898-2903Google Scholar
64Esteller, M. et al. (2000) Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. New England Journal of Medicine 343, 1350-1354Google Scholar
65Toyota, M. et al. (2003) Epigenetic inactivation of CHFR in human tumors. Proceedings of the National Academy of Sciences of the United States of America 100, 7818-7823CrossRefGoogle ScholarPubMed
66Satoh, A. et al. (2003) Epigenetic inactivation of CHFR and sensitivity to microtubule inhibitors in gastric cancer. Cancer Research 63, 8606-8613Google Scholar
67Tada, Y. et al. (2002) The association of death-associated protein kinase hypermethylation with early recurrence in superficial bladder cancers. Cancer Research 62, 4048-4053Google ScholarPubMed
68Figueroa, M.E. et al. (2010) DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia. Cancer Cell 17, 13-27Google Scholar
69Goto, Y. et al. (2009) Epigenetic profiles distinguish malignant pleural mesothelioma from lung adenocarcinoma. Cancer Research 69, 9073-9082Google Scholar
70Arai, E. et al. (2009) Genome-wide DNA methylation profiles in liver tissue at the precancerous stage and in hepatocellular carcinoma. International Journal of Cancer 125, 2854-2862Google Scholar
71Issa, J.P. and Kantarjian, H.M. (2009) Targeting DNA methylation. Clinical Cancer Research 15, 3938-3946CrossRefGoogle ScholarPubMed
72Toyota, M. et al. (2000) Distinct genetic profiles in colorectal tumors with or without the CpG island methylator phenotype. Proceedings of the National Academy of Sciences of the United States of America 97, 710-715Google Scholar
73van Rijnsoever, M. et al. (2002) Characterisation of colorectal cancers showing hypermethylation at multiple CpG islands. Gut 51, 797-802Google Scholar
74Frazier, M.L. et al. (2003) Association of the CpG island methylator phenotype with family history of cancer in patients with colorectal cancer. Cancer Research 63, 4805-4808Google Scholar
75Ward, R.L. et al. (2004) The CpG island methylator phenotype is not associated with a personal or family history of cancer. Cancer Research 64, 7618-7621CrossRefGoogle ScholarPubMed
76Samowitz, W.S. et al. (2005) Evaluation of a large, population-based sample supports a CpG island methylator phenotype in colon cancer. Gastroenterology 129, 837-845Google Scholar
77Suehiro, Y. et al. (2008) Epigenetic-genetic interactions in the APC/WNT, RAS/RAF, and P53 pathways in colorectal carcinoma. Clinical Cancer Research 14, 2560-2569Google Scholar
78Weisenberger, D.J. et al. (2006) CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer. Nature Genetics 38, 787-793CrossRefGoogle ScholarPubMed
79Ogino, S. et al. (2006) CpG island methylator phenotype (CIMP) of colorectal cancer is best characterised by quantitative DNA methylation analysis and prospective cohort studies. Gut 55, 1000-1006Google Scholar
80Cheng, Y.W. et al. (2008) CpG island methylator phenotype associates with low-degree chromosomal abnormalities in colorectal cancer. Clinical Cancer Research 14, 6005-6013Google Scholar
81Ogino, S. et al. (2007) Molecular correlates with MGMT promoter methylation and silencing support CpG island methylator phenotype-low (CIMP-low) in colorectal cancer. Gut 56, 1564-1571Google Scholar
82Messick, C.A. et al. (2009) Genetic and molecular diversity of colon cancer hepatic metastases. Surgery 146, 227-231Google Scholar
83Hiraoka, S. et al. (2006) Laterally spreading type of colorectal adenoma exhibits a unique methylation phenotype and K-ras mutations. Gastroenterology 131, 379-389Google Scholar
84Park, S.J. et al. (2003) Frequent CpG island methylation in serrated adenomas of the colorectum. American Journal of Pathology 162, 815-822Google Scholar
85Rashid, A. et al. (2001) CpG island methylation in colorectal adenomas. American Journal of Pathology 159, 1129-1135Google Scholar
86O'Brien, M.J. et al. (2004) Hyperplastic (serrated) polyps of the colorectum: relationship of CpG island methylator phenotype and K-ras mutation to location and histologic subtype. American Journal of Surgical Pathology 28, 423-434Google Scholar
87Kambara, T. et al. (2004) BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum. Gut 53, 1137-1144Google Scholar
88Chan, A.O. et al. (2002) Concordant CpG island methylation in hyperplastic polyposis. American Journal of Pathology 160, 529-536Google Scholar
89Oue, N. et al. (2003) DNA methylation of multiple genes in gastric carcinoma: association with histological type and CpG island methylator phenotype. Cancer Science 94, 901-905Google Scholar
90Etoh, T. et al. (2004) Increased DNA methyltransferase 1 (DNMT1) protein expression correlates significantly with poorer tumor differentiation and frequent DNA hypermethylation of multiple CpG islands in gastric cancers. American Journal of Pathology 164, 689-699Google Scholar
91An, C. et al. (2005) Prognostic significance of CpG island methylator phenotype and microsatellite instability in gastric carcinoma. Clinical Cancer Research 11, 656-663CrossRefGoogle ScholarPubMed
92Kaneko, Y. et al. (2003) Distinct methylated profiles in Helicobacter pylori dependent and independent gastric MALT lymphomas. Gut 52, 641-646Google Scholar
93Sinn, D.H. et al. (2009) Methylation and API2/MALT1 fusion in colorectal extranodal marginal zone lymphoma. Modern Pathology 22, 314-320Google Scholar
94Ueki, T. et al. (2000) Hypermethylation of multiple genes in pancreatic adenocarcinoma. Cancer Research 60, 1835-1839Google Scholar
95Lee, S. et al. (2002) Aberrant CpG island methylation of multiple genes in intrahepatic cholangiocarcinoma. American Journal of Pathology 161, 1015-1022Google Scholar
96Shen, L. et al. (2002) DNA methylation and environmental exposures in human hepatocellular carcinoma. Journal of the National Cancer Institute 94, 755-761Google Scholar
97Zhang, C. et al. (2008) CpG island methylator phenotype association with upregulated telomerase activity in hepatocellular carcinoma. International Journal of Cancer 123, 998-1004Google Scholar
98Kim, S.G. et al. (2003) Epigenetic and genetic alterations in duodenal carcinomas are distinct from biliary and ampullary carcinomas. Gastroenterology 124, 1300-1310CrossRefGoogle ScholarPubMed
99Suzuki, M. et al. (2006) Exclusive mutation in epidermal growth factor receptor gene, HER-2, and KRAS, and synchronous methylation of nonsmall cell lung cancer. Cancer 106, 2200-2207Google Scholar
100Liu, Z. et al. (2008) CpG island methylator phenotype involving tumor suppressor genes located on chromosome 3p in non-small cell lung cancer. Lung Cancer 62, 15-22Google Scholar
101Suzuki, M. et al. Molecular characterization of chronic obstructive pulmonary disease-related non-small cell lung cancer through aberrant methylation and alterations of EGFR signaling. Annals of Surgical Oncology 17, 878-888Google Scholar
102Abe, M. et al. (2005) CpG island methylator phenotype is a strong determinant of poor prognosis in neuroblastomas. Cancer Research 65, 828-834Google Scholar
103Roman-Gomez, J. et al. (2005) Lack of CpG island methylator phenotype defines a clinical subtype of T-cell acute lymphoblastic leukemia associated with good prognosis. Journal of Clinical Oncology 23, 7043-7049CrossRefGoogle ScholarPubMed
104Arnold, C.N. et al. (2008) Molecular characteristics and predictors of survival in patients with malignant neuroendocrine tumors. International Journal of Cancer 123, 1556-1564CrossRefGoogle ScholarPubMed
105Geli, J. et al. (2008) Global and regional CpG methylation in pheochromocytomas and abdominal paragangliomas: association to malignant behavior. Clinical Cancer Research 14, 2551-2559Google Scholar
106Cohen, Y. et al. (2008) Hypermethylation of CpG island loci of multiple tumor suppressor genes in retinoblastoma. Experimental Eye Research 86, 201-206Google Scholar
107Merhavi, E. et al. (2007) Promoter methylation status of multiple genes in uveal melanoma. Investigative Ophthalmology and Visual Science 48, 4403-4406Google Scholar
Issa, J.P. and Kantarjian, H.M. (2009) Targeting DNA methylation. Clinical Cancer Research 15, 3938-3946Google Scholar
Laird, P.W. (2010) Principles and challenges of genome-wide DNA methylation analysis. Nature Reviews Genetics 11, 191-203Google Scholar
Issa, J.P. and Kantarjian, H.M. (2009) Targeting DNA methylation. Clinical Cancer Research 15, 3938-3946Google Scholar
Laird, P.W. (2010) Principles and challenges of genome-wide DNA methylation analysis. Nature Reviews Genetics 11, 191-203Google Scholar
Issa, J.P. and Kantarjian, H.M. (2009) Targeting DNA methylation. Clinical Cancer Research 15, 3938-3946Google Scholar
Laird, P.W. (2010) Principles and challenges of genome-wide DNA methylation analysis. Nature Reviews Genetics 11, 191-203Google Scholar