Locally Disordered Methylation Forms the Basis of Intratumor Methylome Variation in Chronic Lymphocytic Leukemia
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Lander_Locally disordered.pdf
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Author(s)
Landau, Dan A.
Clement, Kendell
Ziller, Michael J.
Boyle, Patrick
Fan, Jean
Gu, Hongcang
Stevenson, Kristen
Sougnez, Carrie
Wang, Lili
Li, Shuqiang
Date Issued
December 2014
Journal
Cancer Cell
Publisher
Elsevier
Citation
Landau, Dan A. et al. “Locally Disordered Methylation Forms the Basis of Intratumor Methylome Variation in Chronic Lymphocytic Leukemia.” Cancer Cell 26.6 (2014): 813–825.
Version
Author's final manuscript
Abstract
Intratumoral heterogeneity plays a critical role in tumor evolution. To define the contribution of DNA methylation to heterogeneity within tumors, we performed genome-scale bisulfite sequencing of 104 primary chronic lymphocytic leukemias (CLLs). Compared with 26 normal B cell samples, CLLs consistently displayed higher intrasample variability of DNA methylation patterns across the genome, which appears to arise from stochastically disordered methylation in malignant cells. Transcriptome analysis of bulk and single CLL cells revealed that methylation disorder was linked to low-level expression. Disordered methylation was further associated with adverse clinical outcome. We therefore propose that disordered methylation plays a similar role to that of genetic instability, enhancing the ability of cancer cells to search for superior evolutionary trajectories.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.ccell.2014.10.012
