Abstract
DNA methylation plays important roles in gene regulation and functions. Aberrant methylation, either hypomethylation or hypermethylation, has been reported to cause various diseases, especially cancers. Breast cancer ranked the fifth according to the number of cancer deaths in the world. To systematically characterize the epigenetic modification in breast cancer, we examined the genome-wide methylation profiling in 40 breast cancer cell lines. We identified a gene signature consisting of 345 differentially methylated genes, which could be used to discriminate estrogen receptor (ER)-negative and ER-positive breast cancer cell lines. This gene signature is promising for diagnosis and therapies of breast cancer. In the follow up functional analysis of this gene signature, three enriched networks could be highlighted. Interestingly, one of these networks contained estrogen receptor, implying its functional importance of ER-centric module. Finally, we examined the correlation between methylation and expression of these breast cancer cell lines. Very few genes showed significant correlation, suggesting that gene expression regulated by methylation is a complex biological process.
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References
Putti, T.C., El-Rehim, D.M., Rakha, E.A., Paish, C.E., Lee, A.H., Pinder, S.E., Ellis, I.O.: Estrogen Receptor-negative Breast Carcinomas: a Review of Morphology and Immunophenotypical Analysis. Mod. Pathol. 18(1), 26–35 (2005)
Antequera, F.: Structure, Function and Evolution of CpG Island Promoters. Cell Mol. Life Sci. 60(8), 1647–1658 (2003)
Jones, P.A., Baylin, S.B.: The Fundamental Role of Epigenetic Events in Cancer. Nat. Rev. Genet. 3(6), 415–428 (2002)
Cho, B., Lee, H., Jeong, S., Bang, Y.J., Lee, H.J., Hwang, K.S., Kim, H.Y., Lee, Y.S., Kang, G.H., Jeoung, D.I.: 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 (2003)
Chen, R.Z., Pettersson, U., Beard, C., Jackson-Grusby, L., Jaenisch, R.: DNA Hypomethylation Leads to Elevated Mutation Rates. Nature 395(6697), 89–93 (1998)
Eden, A., Gaudet, F., Waghmare, A., Jaenisch, R.: Chromosomal Instability and Tumors Promoted by DNA Hypomethylation. Science 300(5618), 455 (2003)
Baylin, S.B., Herman, J.G.: DNA Hypermethylation in Tumorigenesis: Epigenetics Joins Genetics. Trends Genet. 16(4), 168–174 (2000)
Sakai, T., Toguchida, J., Ohtani, N., Yandell, D.W., Rapaport, J.M., Dryja, T.P.: Allele-specific Hypermethylation of the Retinoblastoma Tumor-suppressor Gene. Am. J. Hum. Genet. 48(5), 880–888 (1991)
Ito, Y., Koessler, T., Ibrahim, A.E., Rai, S., Vowler, S.L., Abu-Amero, S., Silva, A.L., Maia, A.T., Huddleston, J.E., Uribe-Lewis, S., et al.: Somatically Acquired Hypomethylation of IGF2 in Breast and Colorectal Cancer. Hum. Mol. Genet. 17(17), 2633–2643 (2008)
Fernandez, S.V., Snider, K.E., Wu, Y.Z., Russo, I.H., Plass, C., Russo, J.: DNA- Methylation Changes in a Human Cell Model of Breast Cancer Progression. Mutat. Res. (2010) (Advanced online)
Laird, P.W.: Principles and Challenges of Genome-wide DNA Methylation Analysis. Nat. Rev. Genet. 11(3), 191–203 (2010)
Sun, S., Yan, P.S., Huang, T.H., Lin, S.: Identifying Differentially Methylated Genes Using Mixed Effect and Generalized Least Square Models. BMC Bioinformatics 10, 404 (2009)
Guo, A.Y., Sun, J., Riley, B.P., Thiselton, D.L., Kendler, K.S., Zhao, Z.: The Dystrobrevin-binding Protein 1 Gene: features and networks. Mol. Psychiatry 14(1), 18–29 (2009)
Neve, R.M., Chin, K., Fridlyand, J., Yeh, J., Baehner, F.L., Fevr, T., Clark, L., Bayani, N., Coppe, J.P., Tong, F., et al.: A Collection of Breast Cancer Cell Lines for the Study of Functionally Distinct Cancer Subtypes. Cancer Cell 10(6), 515–527 (2006)
Gazdar, A.F., Kurvari, V., Virmani, A., Gollahon, L., Sakaguchi, M., Westerfield, M., Kodagoda, D., Stasny, V., Cunningham, H.T.: Wistuba, II et al: Characterization of Paired Tumor and Non-tumor Cell Lines Established from Patients with Breast Cancer. Int. J. Cancer 78(6), 766–774 (1998)
Klein, C.B., Costa, M.: DNA Methylation and Gene Expression: Introduction and Overview. Mutat. Res. 386(2), 103–105 (1997)
Flanagan, J.M., Cocciardi, S., Waddell, N., Johnstone, C.N., Marsh, A., Henderson, S., Simpson, P., Silva, L., Khanna, K., Lakhani, S., et al.: DNA Methylome of Familial Breast Cancer Identifies Distinct Profiles Defined by Mutation Status. Am. J. Hum. Genet. 86(3), 420–433 (2010)
Metzker, M.L.: Sequencing Technologies - the Next Generation. Nat. Rev. Genet. 11(1), 31–46 (2010)
Clarke, J., Wu, H.C., Jayasinghe, L., Patel, A., Reid, S., Bayley, H.: Continuous Base Identification for Single-molecule Nanopore DNA Sequencing. Nat. Nanotechnol. 4(4), 265–270 (2009)
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Han, L., Zheng, S., Sun, S., Huang, T.H., Zhao, Z. (2010). Genome-Wide DNA Methylation Profiling in 40 Breast Cancer Cell Lines. In: Huang, DS., Zhao, Z., Bevilacqua, V., Figueroa, J.C. (eds) Advanced Intelligent Computing Theories and Applications. ICIC 2010. Lecture Notes in Computer Science, vol 6215. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-14922-1_35
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DOI: https://doi.org/10.1007/978-3-642-14922-1_35
Publisher Name: Springer, Berlin, Heidelberg
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