Abstract
The Cancer Genome Atlas (TCGA) epigenome data includes the DNA methylation status of tumor and normal tissues of large cohorts for dozens of cancer types. Due to the moderately large data sizes, retrieving and analyzing them requires basic programming skills. Simple data browsing (e.g., candidate gene search) is hampered by the scarcity of easy-to-use data browsers addressed to the broad community of biomedical researchers. We propose a new visualization method depicting the overall DNA methylation status at each TCGA cohort while emphasizing its heterogeneity, thus facilitating the evaluation of the cohort variability and the normal versus tumor differences. Implemented as a trackhub integrated to the University of California Santa Cruz (UCSC) genome browser, it can be easily added to any genome-wide annotation layer.
To exemplify the trackhub usage we evaluate local DNA methylation boundaries, the aberrant DNA methylation of a CpG island located at the estrogen receptor 1 (ESR1) in breast and colon cancer, and the hypermethylation of the Homeobox HOXA gene cluster and the EN1 gene in multiple cancer types. The DNA methylation pancancer trackhub is freely available at http://maplab.cat/tcga_450k_trackhub.
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References
Zhang J, Baran J, Cros A, Guberman JM, Haider S, Hsu J, Liang Y, Rivkin E, Wang J, Whitty B, Wong-Erasmus M, Yao L, Kasprzyk A (2011) International Cancer Genome Consortium Data Portal—a one-stop shop for cancer genomics data. Database (Oxford) 2011:bar026
Schroeder MP, Gonzalez-Perez A, Lopez-Bigas N (2013) Visualizing multidimensional cancer genomics data. Genome Med 5(1):9
Cerami E, Gao J, Dogrusoz U, Gross BE, Sumer SO, Aksoy BA, Jacobsen A, Byrne CJ, Heuer ML, Larsson E, Antipin Y, Reva B, Goldberg AP, Sander C, Schultz N (2012) The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2(5):401–404
Cline MS, Craft B, Swatloski T, Goldman M, Ma S, Haussler D, Zhu J (2013) Exploring TCGA Pan-Cancer data at the UCSC Cancer Genomics Browser. Sci Rep 3:2652
Speir ML, Zweig AS, Rosenbloom KR, Raney BJ, Paten B, Nejad P, Lee BT, Learned K, Karolchik D, Hinrichs AS, Heitner S, Harte RA, Haeussler M, Guruvadoo L, Fujita PA, Eisenhart C, Diekhans M, Clawson H, Casper J, Barber GP, Haussler D, Kuhn RM, Kent WJ (2016) The UCSC Genome Browser database: 2016 update. Nucleic Acids Res 44(D1):D717–D725
Bibikova M, Barnes B, Tsan C, Ho V, Klotzle B, Le JM, Delano D, Zhang L, Schroth GP, Gunderson KL, Fan JB, Shen R (2011) High density DNA methylation array with single CpG site resolution. Genomics 98(4):288–295
Zhu Y, Qiu P, Ji Y (2014) TCGA-assembler: open-source software for retrieving and processing TCGA data. Nat Methods 11(6):599–600
Esteller M (2007) Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet 8(4):286–298
Muller HM, Widschwendter A, Fiegl H, Ivarsson L, Goebel G, Perkmann E, Marth C, Widschwendter M (2003) DNA methylation in serum of breast cancer patients: an independent prognostic marker. Cancer Res 63(22):7641–7645
Frigola J, Song J, Stirzaker C, Hinshelwood RA, Peinado MA, Clark S (2006) Epigenetic remodeling in colorectal cancer results in coordinate gene suppression across an entire chromosome band. Nat Genet 38(5):540–549
Rauch T, Wang Z, Zhang X, Zhong X, Wu X, Lau SK, Kernstine KH, Riggs AD, Pfeifer GP (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):5527–5532
Mayor R, Casadome L, Azuara D, Moreno V, Clark SJ, Capella G, Peinado MA (2009) Long-range epigenetic silencing at 2q14.2 affects most human colorectal cancers and may have application as a non-invasive biomarker of disease. Br J Cancer 100(10):1534–1539
Acknowledgments
We thank Iñaki Martinez de Ilarduya for his excellent technical support. The trackhub published here is based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/. This work was supported by the Spanish Ministry of Economy and Competitiveness [SAF2011/23638 and SAF2015-64521-R to M.A.P.]. CERCA Program/Generalitat de Catalunya.
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Mallona, I., Sierco, A., Peinado, M.A. (2018). The Pancancer DNA Methylation Trackhub: A Window to The Cancer Genome Atlas Epigenomics Data. In: Vavouri, T., Peinado, M. (eds) CpG Islands. Methods in Molecular Biology, vol 1766. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7768-0_7
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DOI: https://doi.org/10.1007/978-1-4939-7768-0_7
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