The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Increased methylation variation in epigenetic domains across cancer types
Open accessAbstract
Tumor heterogeneity is a major barrier to effective cancer diagnosis and treatment. We recently identified cancer-specific differentially DNA-methylated regions (cDMRs) in colon cancer, which also distinguish normal tissue types from each other, suggesting that these cDMRs might be generalized across cancer types. Here we show stochastic methylation variation of the same cDMRs, distinguishing cancer from normal tissue, in colon, lung, breast, thyroid and Wilms' tumors, with intermediate variation in adenomas. Whole-genome bisulfite sequencing shows these variable cDMRs are related to loss of sharply delimited methylation boundaries at CpG islands. Furthermore, we find hypomethylation of discrete blocks encompassing half the genome, with extreme gene expression variability. Genes associated with the cDMRs and large blocks are involved in mitosis and matrix remodeling, respectively. We suggest a model for cancer involving loss of epigenetic stability of well-defined genomic domains that underlies increased methylation variability in cancer that may contribute to tumor heterogeneity.
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Cites
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Self-citationThe fundamental role of epigenetic events in cancer
Jones, P. A., & Baylin, S. B. (2002) · Nature Reviews Genetics · doi:10.1038/nrg816 · Cited by 5,648
Human DNA methylomes at base resolution show widespread epigenomic differences
Lister, R., Pelizzola, M., Dowen, R. H., Hawkins, R. D., Hon, G., Tonti-Filippini, J., Nery, J. R., Lee, L., Ye, Z., Ngo, Q.-M., et al. (2009) · Nature · doi:10.1038/nature08514 · Cited by 4,673
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The history of cancer epigenetics
Feinberg, A. P., & Tycko, B. (2004) · Nature Reviews Cancer · doi:10.1038/nrc1279 · Cited by 2,344
Self-citationCircular binary segmentation for the analysis of array-based DNA copy number data
Olshen, A. B., Venkatraman, E. S., Lucito, R., & Wigler, M. (2004) · Biostatistics · doi:10.1093/biostatistics/kxh008 · Cited by 2,325
Tackling the widespread and critical impact of batch effects in high-throughput data
Leek, J. T., Scharpf, R. B., Bravo, H. C., Simcha, D., Langmead, B., Johnson, W. E., Geman, D., Baggerly, K., & Irizarry, R. A. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2825 · Cited by 2,196
Self-citationIrizarry, R. A., Ladd-Acosta, C., Wen, B., Wu, Z., Montano, C., Onyango, P., Cui, H., Gabo, K., Rongione, M., Webster, M., et al. (2009) · Nature Genetics · doi:10.1038/ng.298 · Cited by 2,177
Self-citationUsing GOstats to test gene lists for GO term association
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DNA methylation in cancer: too much, but also too little
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Cited by
Genomic and Epigenomic Landscapes of Adult De Novo Acute Myeloid Leukemia
The Cancer Genome Atlas Research Network (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1301689 · Cited by 5,078
A decade of exploring the cancer epigenome—biological and translational implications
Baylin, S. B., & Jones, P. A. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3130 · Cited by 2,871
Epigenetic plasticity and the hallmarks of cancer
Flavahan, W. A., Gaskell, E., & Bernstein, B. E. (2017) · Science · doi:10.1126/science.aal2380 · Cited by 1,340
“DNAmethylation instability has also been linked to stochastic activation of cancer-associated genes that are stably repressed in non-neoplastic tissue, including cell cycle–related and epithelialmesenchymal transition–related genes (71).”
BackgroundEpigenetic Determinants of Cancer
Baylin, S. B., & Jones, P. A. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a019505 · Cited by 1,226
Cancer Epigenetics: Tumor Heterogeneity, Plasticity of Stem-like States, and Drug Resistance
Easwaran, H., Tsai, H.-C., & Baylin, S. B. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.05.015 · Cited by 915
Metadata
- Authors
- Hansen, K. D., Timp, W., Bravo, H. C., Sabunciyan, S., Langmead, B., McDonald, O. G., Wen, B., Wu, H., Liu, Y., Diep, D., Briem, E., Zhang, K., Irizarry, R. A., & Feinberg, A. P.
- Venue
- Nature Genetics
- Published
- 2011-06-26
- Volume
- 43
- Issue
- 8
- Pages
- 768-775
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2125154191
- Cited by
- 1,045
- References
- 40
- FWCI
- 40.68
- Type
- journal article
- Language
- en
- Open access
- green
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- Hansen, K. D., Timp, W., Bravo, H. C., Sabunciyan, S., Langmead, B., McDonald, O. G., Wen, B., Wu, H., Liu, Y., Diep, D., Briem, E., Zhang, K., Irizarry, R. A., & Feinberg, A. P. (2011). Increased methylation variation in epigenetic domains across cancer types. Nature Genetics. https://doi.org/10.1038/ng.865
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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