Summary
It is now apparent that epigenetic abnormalities, in particular altered DNA methylation, play a crucial role in the development and progression of human cancers. DNA hypermethylation at promoter CpG islands is now recognized as a third mechanism by which inactivation of tumor suppressor genes occurs. Aberrant CpG island hypermethylation is also frequently observed in chronic inflammation and precancerous lesions, which suggests that it is an early event in tumorigenesis that could serve as a useful tumor marker. A variety of screening techniques have been developed for genome-wide screening of methylation status. Of those, transcriptome analysis coupled with pharmacological unmasking has emerged as a powerful tool for revealing DNA methylation patterns in cancer cells and identifying new tumor marker candidates.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Herman, J. G., and Baylin, S. B. (2003) Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med 349, 2042–54.
Baylin, S. B., and Ohm, J. E. (2006) Epige-netic gene silencing in cancer – a mechanism for early oncogenic pathway addiction? Nat Rev Cancer 6, 107–16.
Esteller, M. (2007) Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet 8, 286–98.
Takai, D., and Jones, P. A. (2002) Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc Natl Acad Sci U S A 99, 3740–5.
Feinberg, A. P., and Tycko, B. (2004) The history of cancer epigenetics. Nat Rev Cancer 4, 143–53.
Eads, C. A., Lord, R. V., Kurumboor, S. K., Wickramasinghe, K., Skinner, M. L., Long, T. I., Peters, J. H., DeMeester, T. R., Danen-berg, K. D., Danenberg, P. V., Laird, P. W., and Skinner, K. A. (2000) Fields of aberrant CpG island hypermethylation in Barrett's esophagus and associated adenocarcinoma. Cancer Res 60, 5021–26.
Schulmann, K., Sterian, A., Berki, A., Yin, J., Sato, F., Xu, Y., Olaru, A., Wang, S., Mori, Y., Deacu, E., Hamilton, J., Kan, T., Krasna, M. J., Beer, D. G., Pepe, M. S., Abraham, J. M., Feng, Z., Schmiegel, W., Greenwald, B. D., and Meltzer, S. J. (2005) Inactivation of p16, RUNX3, and HPP1 occurs early in Barrett's-associated neoplastic progression and predicts progression risk. Oncogene 24, 4138–48.
Kang, G. H., Lee, H. J., Hwang, K. S., Lee, S., Kim, J. H., and Kim, J. S. (2003) Aberrant CpG island hypermethylation of chronic gastritis, in relation to aging, gender, intestinal metaplasia, and chronic inflammation. Am J Pathol 163, 1551–6.
Chan, A. O., Lam, S. K., Wong, B. C., Wong, W. M., Yuen, M. F., Yeung, Y. H., Hui, W. M., Rashid, A., and Kwong, Y. L. (2003) Promoter methylation of E-cadherin gene in gastric mucosa associated with Helicobacter pylori infection and in gastric cancer. Gut 52, 502–6.
Maekita, T., Nakazawa, K., Mihara, M., Naka-jima, T., Yanaoka, K., Iguchi, M., Arii, K., Kaneda, A., Tsukamoto, T., Tatematsu, M., Tamura, G., Saito, D., Sugimura, T., Ichinose, M., and Ushijima, T. (2006) High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res 12, 989–95.
Kaneto, H., Sasaki, S., Yamamoto, H., Itoh, F., Toyota, M., Suzuki, H., Ozeki, I., Iwata, N., Ohmura, T., Satoh, T., Karino, Y., Satoh, T., Toyota, J., Satoh, M., Endo, T., Omata, M., and Imai, K. (2001) Detection of hypermeth-ylation of the p16(INK4A) gene promoter in chronic hepatitis and cirrhosis associated with hepatitis B or C virus. Gut 48, 372–7.
Issa, J. P. , Ahuja, N., Toyota, M., Bronner, M. P., and Brentnall, T. A. (2001) Accelerated age-related CpG island methylation in ulcerative colitis. Cancer Res 61, 3573–7.
Sato, F., Harpaz, N., Shibata, D., Xu, Y., Yin, J., Mori, Y., Zou, T. T., Wang, S., Desai, K., Leytin, A., Selaru, F. M., Abraham, J. M., and Meltzer, S. J. (2002) Hypermethylation of the p14(ARF) gene in ulcerative colitis-associated colorectal carcinogenesis. Cancer Res 62, 1148–51.
Sato, F., Shibata, D., Harpaz, N., Xu, Y., Yin, J., Mori, Y., Wang, S., Olaru, A., Deacu, E., Selaru, F. M., Kimos, M. C., Hytiroglou, P., Young, J., Leggett, B., Gazdar, A. F., Toyooka, S., Abraham, J. M., and Meltzer, S. J. (2002) Aberrant methylation of the HPP1 gene in ulcerative colitis-associated colorectal carcinoma. Cancer Res 62, 6820–2.
Laird, P. W. (2003) The power and the promise of DNA methylation markers. Nat Rev Cancer 3, 253–66.
Ushijima, T. (2005) Detection and interpretation of altered methylation patterns in cancer cells. Nat Rev Cancer 5, 223–31.
Toyota, M., Ho, C., Ahuja, N., Jair, K. W., Li, Q., Ohe-Toyota, M., Baylin, S. B., and Issa, J. P. (1999) Identification of differentially methylated sequences in colorectal cancer by methylated CpG island amplification. Cancer Res 59, 2307–12.
Costello, J. F., Frühwald, M. C., Smiraglia, D. J., Rush, L. J., Robertson, G. P., Gao, X., Wright, F. A., Feramisco, J. D., Peltomäki, P., Lang, J. C., Schuller, D. E., Yu, L., Bloomfield, C. D., Caligiuri, M. A., Yates, A., Nishikawa, R., Su Huang, H., Petrelli, N. J., Zhang, X., O'Dorisio, M. S., Held, W. A., Cavenee, W. K., and Plass, C. (2000) Aberrant CpG-island methylation has non-random and tumour-type-specific patterns. Nat Genet 24, 132–8.
Yamashita, K., Dai, T., Dai, Y., Yamamoto, F., and Perucho, M. (2003) Genetics supersedes epigenetics in colon cancer phenotype. Cancer Cell 4, 121–31.
Suzuki, H., Gabrielson, E., Chen, W., Anbazhagan, R., van Engeland, M., Weijen-berg, M. P., Herman, J. G., and Baylin, S. B. (2002) A genomic screen for genes upregu-lated by demethylation and histone deacety-lase inhibition in human colorectal cancer. Nat Genet 31, 141–9.
Yamashita, K., Upadhyay, S., Osada, M., Hoque, M. O., Xiao, Y., Mori, M., Sato, F., Meltzer, S. J., and Sidransky, D. (2002) Pharmacologic unmasking of epigenetically silenced tumor suppressor genes in esopha-geal squamous cell carcinoma. Cancer Cell 2, 485–95.
Sato, N., Fukushima, N., Maitra, A., Matsuba-yashi, H., Yeo, C. J., Cameron, J. L., Hruban, R. H., and Goggins, M. (2003) Discovery of novel targets for aberrant methylation in pancreatic carcinoma using high-throughput microarrays. Cancer Res 63, 3735–42.
Schuebel, K. E., Chen, W., Cope, L., Glock-ner, S. C., Suzuki, H., Yi, J. M., Chan, T. A., Neste, L. V., Criekinge, W. V., Bosch, S. V., van Engeland, M., Ting, A. H., Jair, K., Yu, W., Toyota, M., Imai, K., Ahuja, N., Herman, J. G., and Baylin, S. B. (2007) Comparing the DNA hypermethylome with gene mutations in human colorectal cancer. PLoS Genet 3, e157.
Herman, J. G., Graff, J. R., Myohanen, S., Nelkin, B. D., and Baylin, S. B. (1996) Meth-ylation-specific PCR: a novel PCR assay for methylation status of CpG islands. Proc Natl Acad Sci U S A 93, 9821–6.
Xiong, Z., and Laird, P. W. (1997) COBRA: a sensitive and quantitative DNA methylation assay. Nucleic Acids Res 25, 2532–4.
Eads, C. A., Danenberg, K. D., Kawakami, K., Saltz, L. B., Blake, C., Shibata, D., Danenberg, P. V., and Laird, P. W. (2000) MethyLight: a high-throughput assay to measure DNA meth-ylation. Nucleic Acids Res 28, E32.
Colella, S., Shen, L., Baggerly, K. A., Issa, J. P., and Krahe, R. (2003) Sensitive and quantitative universal Pyrosequencing methyla-tion analysis of CpG sites. Biotechniques 35, 146–50.
Toyota, M., Sasaki, Y., Satoh, A., Ogi, K., Kikuchi, T., Suzuki, H., Mita, H., Tanaka, N., Itoh, F., Issa, J. P., Jair, K. W., Schuebel, K. E., Imai, K., and Tokino, T. (2003) Epigenetic inactivation of CHFR in human tumors. Proc Natl Acad Sci U S A 100, 7818–23.
Taniguchi, H., Yamamoto, H., Hirata, T., Miyamoto, N., Oki, M., Nosho, K., Adachi, Y., Endo, T., Imai, K., and Shinomura, Y. (2005) Frequent epigenetic inactivation of Wnt inhibitory factor-1 in human gastrointestinal cancers. Oncogene 24, 7946–52.
Sato, H., Suzuki, H., Toyota, M., Nojima, M., Maruyama, R., Sasaki, S., Takagi, H., Sogabe, Y. , Sasaki, Y., Idogawa, M., Sonoda, T., Mori, M., Imai, K., Tokino, T., and Shinomura, Y. (2007) Frequent epigenetic inactivation of DICKKOPF family genes in human gastrointestinal tumors. Carcinogenesis 28, 2459–66.
Cameron, E. E., Bachman, K. E., Myohanen, S., Herman, J. G., and Baylin, S. B. (1999) Synergy of demethylation and histone deacety-lase inhibition in the re-expression of genes silenced in cancer. Nat Genet 21, 103–7.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Springer Science + Business Media, LLC
About this protocol
Cite this protocol
Suzuki, H., Toyota, M., Kondo, Y., Shinomura, Y. (2009). Inflammation-Related Aberrant Patterns of DNA Methylation: Detection and Role in Epigenetic Deregulation of Cancer Cell Transcriptome. In: Kozlov, S.V. (eds) Inflammation and Cancer. Methods in Molecular Biology™, vol 512. Humana Press. https://doi.org/10.1007/978-1-60327-530-9_5
Download citation
DOI: https://doi.org/10.1007/978-1-60327-530-9_5
Publisher Name: Humana Press
Print ISBN: 978-1-60327-529-3
Online ISBN: 978-1-60327-530-9
eBook Packages: Springer Protocols