Abstract
Epigenetics is the study of informationmaintained duringmitotic division other than the DNA sequence itself and includes DNA methylation, and modifi- cation of chromatin histone tails. Both DNA methylation and chromatin structure are essential to normal growth and development in mammals and regulate diverse functions such as imprinting, genomic stability, and gene transcription. Incorrect establishment, maintenance, or recognition of epigenetic marks can lead to a wide range of human diseases including immunodeficiency, centromeric region instability and facial anomalies syndrome (ICF), Rett syndrome, and cancer. In human cancer, both global hypomethylation of DNA across the genome and locus specific hypermethylation of DNA in promoters are common, thus are hallmarks of malignancy. Changes in transcription of histone tail modifying enzymes have also been well documented in a variety of human tumors. Although a great deal is known about epigenetic changes in cancer at the single gene level, little is known about the cancer epigenome; a genome-wide approach is likely to reveal important new insights that can not been seen from the single gene viewpoint. In this chapter we will describe new technologies used to study the epigenome and review what we have learned about the cancer epigenome using these new approaches.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Arisan, S., E. D. Buyuktuncer, et al. (2005). “Increased expression of EZH2, a polycomb group protein, in bladder carcinoma.” Urol Int 75(3): 252–7.
Ballestar, E., M. F. Paz, et al. (2003). “Methyl-CpG binding proteins identify novel sites of epigenetic inactivation in human cancer.” EMBO J 22(23): 6335–45.
Barski, A., S. Cuddapah, et al. (2007). “High-resolution profiling of histone methylations in the human genome.” Cell 129(4): 823–37.
Bibikova, M., Z. Lin, et al. (2006). “High-throughput DNA methylation profiling using universal bead arrays.” Genome Res 16(3): 383–93.
Callinan, P. A. and A. P. Feinberg (2006). “The emerging science of epigenomics.” Hum Mol Genet 15 Spec No 1: R95–101.
Cheng, A. S., A. C. Culhane, et al. (2008). “Epithelial progeny of estrogen-exposed breast progenitor cells display a cancer-like methylome.” Cancer Res 68(6): 1786–96.
Cho, B., H. Lee, et al. (2003). “Promoter hypomethylation of a novel cancer/testis antigen gene CAGE is correlated with its aberrant expression and is seen in premalignant stage of gastric carcinoma.” Biochem Biophys Res Commun 307(1): 52–63.
Cillo, C., A. Faiella, et al. (1999). “Homeobox genes and cancer.” Exp Cell Res 248(1): 1–9.
Clark, S. J. and J. Melki (2002). “DNA methylation and gene silencing in cancer: which is the guilty party?” Oncogene 21(35): 5380–7.
Costello, J. F., M. C. Fruhwald, et al. (2000). “Aberrant CpG-island methylation has non-random and tumour-type-specific patterns.” Nat Genet 24(2): 132–8.
Croonquist, P. A. and B. Van Ness (2005). “The polycomb group protein enhancer of zeste homolog 2 (EZH 2) is an oncogene that influences myeloma cell growth and the mutant ras phenotype.” Oncogene 24(41): 6269–80.
Eads, C. A., K. D. Danenberg, et al. (2000). “MethyLight: a high-throughput assay to measure DNA methylation.” Nucleic Acids Res 28(8): E32.
Eckhardt, F., J. Lewin, et al. (2006). “DNA methylation profiling of human chromosomes 6, 20 and 22.” Nat Genet 38(12): 1378–85.
Ehrbrecht, A., U. Muller, et al. (2006). “Comprehensive genomic analysis of desmoplastic medulloblastomas: identification of novel amplified genes and separate evaluation of the different histological components.” J Pathol 208(4): 554–63.
Estecio, M. R., P. S. Yan, et al. (2007). “High-throughput methylation profiling by MCA coupled to CpG island microarray.” Genome Res 17(10): 1529–36.
Fahrner, J. A., S. Eguchi, et al. (2002). “Dependence of histone modifications and gene expression on DNA hypermethylation in cancer.” Cancer Res 62(24): 7213–8.
Feinberg, A.P. (2001). “Methylation meets genomics.” Nat Genet 27(1): 9–10.
Feinberg, A. P. and B. Tycko (2004). “The history of cancer epigenetics.” Nat Rev Cancer 4(2): 143–53.
Feinberg, A. P. and B. Vogelstein (1983). “Hypomethylation distinguishes genes of some human cancers from their normal counterparts.” Nature 301(5895): 89–92.
Figueroa, M. E., M. Reimers, et al. (2008). “An integrative genomic and epigenomic approach for the study of transcriptional regulation.” PLoS ONE 3(3): e1882.
Fraga, M. F., E. Ballestar, et al. (2005). “Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer.” Nat Genet 37(4): 391–400.
Gama-Sosa, M. A., V. A. Slagel, et al. (1983). “The 5-methylcytosine content of DNA from human tumors.” Nucleic Acids Res 11(19): 6883–94.
Guidi, C. J., A. T. Sands, et al. (2001). “Disruption of Ini1 leads to peri-implantation lethality and tumorigenesis in mice.” Mol Cell Biol 21(10): 3598–603.
Hake, S. B., A. Xiao, et al. (2004).v“Linking the epigenetic ‘language’ of covalent histone modifications to cancer.” Br J Cancer 90(4): 761–9.
Hatada, I., M. Fukasawa, et al. (2006). “Genome-wide profiling of promoter methylation in human.” Oncogene 25(21): 3059–64.
Herman, J. G., J. R. Graff, et al. (1996). “Methylation-specific PCR: a novel PCR assay for methylation status of CpG islands.” Proc Natl Acad Sci U S A 93(18): 9821–6.
Hoemme, C., A. Peerzada, et al. (2008). “Chromatin modifications induced by PML-RARalpha repress critical targets in leukemogenesis as analyzed by ChIP-Chip.” Blood 111(5): 2887–95.
Hu, M., J. Yao, et al. (2005). “Distinct epigenetic changes in the stromal cells of breast cancers.” Nat Genet 37(8): 899–905.
Hu, M., J. Yao, et al. (2006). “Methylation-specific digital karyotyping.” Nat Protoc 1(3): 1621–36.
Illingworth, R., A. Kerr, et al. (2008). “A novel CpG island set identifies tissue-specific methylation at developmental gene loci.” PLoS Biol 6(1): e22.
Irizarry, R. A., C. Ladd-Acosta, et al. (2008). “Comprehensive high-throughput arrays for relative methylation (CHARM).” Genome Res 18(5): 780–90.
Italiano, A., R. Attias, et al. (2006). “Molecular cytogenetic characterization of a metastatic lung sarcomatoid carcinoma: 9p23 neocentromere and 9p23-p24 amplification including JAK2 and JMJD2C.” Cancer Genet Cytogenet 167(2): 122–30.
Kleer, C. G., Q. Cao, et al. (2003). “EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells.” Proc Natl Acad Sci U S A 100(20): 11606–11.
Klochendler-Yeivin, A., L. Fiette, et al. (2000). “The murine SNF5/INI1 chromatin remodeling factor is essential for embryonic development and tumor suppression.” EMBO Rep 1(6): 500–6.
Mutskov, V. and G. Felsenfeld (2004). “Silencing of transgene transcription precedes methylation of promoter DNA and histone H3 lysine 9.” EMBO J 23(1): 138–49.
Nakamura, N. and K. Takenaga (1998). “Hypomethylation of the metastasis-associated S100A4 gene correlates with gene activation in human colon adenocarcinoma cell lines.” Clin Exp Metastasis 16(5): 471–9.
Rauch, T., H. Li, 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 Res 66(16): 7939–47.
Rauch, T. and G. P. Pfeifer (2005). “Methylated-CpG island recovery assay: a new technique for the rapid detection of methylated-CpG islands in cancer.” Lab Invest 85(9): 1172–80.
Rauch, T., Z. Wang, et al. (2007). “Homeobox gene methylation in lung cancer studied by genome-wide analysis with a microarray-based methylated CpG island recovery assay.” Proc Natl Acad Sci U S A 104(13): 5527–32.
Roberts, C. W., S. A. Galusha, et al. (2000). “Haploinsufficiency of Snf5 (integrase interactor 1) predisposes to malignant rhabdoid tumors in mice.” Proc Natl Acad Sci U S A 97(25): 13796–800.
Rosty, C., T. Ueki, et al. (2002). “Overexpression of S100A4 in pancreatic ductal adenocarcinomas is associated with poor differentiation and DNA hypomethylation.” Am J Pathol 160(1): 45–50.
Scholz, C., I. Nimmrich, et al. (2005). “Distinction of acute lymphoblastic leukemia from acute myeloid leukemia through microarray-based DNA methylation analysis.” Ann Hematol 84(4): 236–44.
Shen, L., Y. Kondo, et al. (2007). “Genome-wide profiling of DNA methylation reveals a class of normally methylated CpG island promoters.” PLoS Genet 3(10): 2023–36.
Stirzaker, C., J. Z. Song, et al. (2004). “Transcriptional gene silencing promotes DNA hypermethylation through a sequential change in chromatin modifications in cancer cells.” Cancer Res 64(11): 3871–7.
Sutherland, E., L. Coe, et al. (1992). “McrBC: a multisubunit GTP-dependent restriction endonuclease.” J Mol Biol 225(2): 327–48.
Tokizane, T., H. Shiina, et al. (2005). “Cytochrome P450 1B1 is overexpressed and regulated by hypomethylation in prostate cancer.” Clin Cancer Res 11(16): 5793–801.
Tomonaga, T., K. Matsushita, et al. (2003). “Overexpression and mistargeting of centromere protein-A in human primary colorectal cancer.” Cancer Res 63(13): 3511–6.
Varambally, S., S. M. Dhanasekaran, et al. (2002). “The polycomb group protein EZH2 is involved in progression of prostate cancer.” Nature 419(6907): 624–9.
Versteege, I., N. Sevenet, et al. (1998). “Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer.” Nature 394(6689): 203–6.
Visser, H. P., M. J. Gunster, et al. (2001). “The Polycomb group protein EZH2 is upregulated in proliferating, cultured human mantle cell lymphoma.” Br J Haematol 112(4): 950–8.
Wang, G. G., C. D. Allis, et al. (2007). “Chromatin remodeling and cancer, Part I: Covalent histone modifications.” Trends Mol Med 13(9): 363–72.
Wang, G. G., C. D. Allis, et al. (2007). “Chromatin remodeling and cancer, Part II: ATP-dependent chromatin remodeling.” Trends Mol Med 13(9): 373–80.
Weber, M., J. J. Davies, et al. (2005). “Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells.” Nat Genet 37(8): 853–62.
Wu, H., Y. Chen, et al. (2005). “Hypomethylation-linked activation of PAX2 mediates tamoxifen-stimulated endometrial carcinogenesis.” Nature 438(7070): 981–7.
Xie, R., D. S. Loose, et al. (2007). “Hypomethylation-induced expression of S100A4 in endometrial carcinoma.” Mod Pathol 20(10): 1045–54.
Yang, Z. Q., I. Imoto, et al. (2000). “Identification of a novel gene, GASC1, within an amplicon at 9p23–24 frequently detected in esophageal cancer cell lines.” Cancer Res 60(17): 4735–9.
Ye, L., X. Li, et al. (2005). “Hypomethylation in the promoter region of POMC gene correlates –with ectopic overexpression in thymic carcinoids.” J Endocrinol 185(2): 337–43.
Yu, J., D. R. Rhodes, et al. (2007). “A polycomb repression signature in metastatic prostate cancer predicts cancer outcome.” Cancer Res 67(22): 10657–63.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer Science+Business Media B.V.
About this chapter
Cite this chapter
Ladd-Acosta, C., Feinberg, A.P. (2009). Cancer Epigenomics. In: Ferguson-Smith, A.C., Greally, J.M., Martienssen, R.A. (eds) Epigenomics. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9187-2_21
Download citation
DOI: https://doi.org/10.1007/978-1-4020-9187-2_21
Publisher Name: Springer, Dordrecht
Print ISBN: 978-1-4020-9186-5
Online ISBN: 978-1-4020-9187-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)