Despite much evidence on epigenetic abnormalities in cancer, it is currently unclear to what extent epigenetic alterations can be associated with tumors' clonal genetic origins. Here, we show that the prostate intratumor heterogeneity in DNA methylation and copy-number patterns can be explained by a unified evolutionary process. By assaying multiple topographically distinct tumor sites, premalignant lesions, and lymph node metastases within five cases of prostate cancer, we demonstrate that both DNA methylation and copy-number heterogeneity consistently reflect the life history of the tumors. Furthermore, we show cases of genetic or epigenetic convergent evolution and highlight the diversity in the evolutionary origins and aberration spectrum between tumor and metastatic subclones. Importantly, DNA methylation can complement genetic data by serving as a proxy for activity at regulatory domains, as we show through identification of high epigenetic heterogeneity at androgen-receptor-bound enhancers. Epigenome variation thereby expands on the current genome-centric view on tumor heterogeneity.
Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; The German Cancer Consortium, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Electronic address: c.plass@dkfz.de.
%0 Journal Article
%1 Brocks2014
%A Brocks, David
%A Assenov, Yassen
%A Minner, Sarah
%A Bogatyrova, Olga
%A Simon, Ronald
%A Koop, Christina
%A Oakes, Christopher
%A Zucknick, Manuela
%A Lipka, Daniel Bernhard
%A Weischenfeldt, Joachim
%A Feuerbach, Lars
%A Cowper-Sal Lari, Richard
%A Lupien, Mathieu
%A Brors, Benedikt
%A Korbel, Jan
%A Schlomm, Thorsten
%A Tanay, Amos
%A Sauter, Guido
%A Gerhäuser, Clarissa
%A Plass, Christoph
%A ICGC Early Onset Prostate Cancer Project,
%D 2014
%J Cell Rep
%K ABI-DKFZ
%N 3
%P 798--806
%T Intratumor DNA methylation heterogeneity reflects clonal evolution in aggressive prostate cancer.
%V 8
%X Despite much evidence on epigenetic abnormalities in cancer, it is currently unclear to what extent epigenetic alterations can be associated with tumors' clonal genetic origins. Here, we show that the prostate intratumor heterogeneity in DNA methylation and copy-number patterns can be explained by a unified evolutionary process. By assaying multiple topographically distinct tumor sites, premalignant lesions, and lymph node metastases within five cases of prostate cancer, we demonstrate that both DNA methylation and copy-number heterogeneity consistently reflect the life history of the tumors. Furthermore, we show cases of genetic or epigenetic convergent evolution and highlight the diversity in the evolutionary origins and aberration spectrum between tumor and metastatic subclones. Importantly, DNA methylation can complement genetic data by serving as a proxy for activity at regulatory domains, as we show through identification of high epigenetic heterogeneity at androgen-receptor-bound enhancers. Epigenome variation thereby expands on the current genome-centric view on tumor heterogeneity.
@article{Brocks2014,
__markedentry = {[bbrors:6]},
abstract = {Despite much evidence on epigenetic abnormalities in cancer, it is currently unclear to what extent epigenetic alterations can be associated with tumors' clonal genetic origins. Here, we show that the prostate intratumor heterogeneity in DNA methylation and copy-number patterns can be explained by a unified evolutionary process. By assaying multiple topographically distinct tumor sites, premalignant lesions, and lymph node metastases within five cases of prostate cancer, we demonstrate that both DNA methylation and copy-number heterogeneity consistently reflect the life history of the tumors. Furthermore, we show cases of genetic or epigenetic convergent evolution and highlight the diversity in the evolutionary origins and aberration spectrum between tumor and metastatic subclones. Importantly, DNA methylation can complement genetic data by serving as a proxy for activity at regulatory domains, as we show through identification of high epigenetic heterogeneity at androgen-receptor-bound enhancers. Epigenome variation thereby expands on the current genome-centric view on tumor heterogeneity.},
added-at = {2015-06-29T14:32:37.000+0200},
author = {Brocks, David and Assenov, Yassen and Minner, Sarah and Bogatyrova, Olga and Simon, Ronald and Koop, Christina and Oakes, Christopher and Zucknick, Manuela and Lipka, Daniel Bernhard and Weischenfeldt, Joachim and Feuerbach, Lars and {Cowper-Sal Lari}, Richard and Lupien, Mathieu and Brors, Benedikt and Korbel, Jan and Schlomm, Thorsten and Tanay, Amos and Sauter, Guido and Gerh{\"{a}}user, Clarissa and Plass, Christoph and {ICGC Early Onset Prostate Cancer Project}},
biburl = {https://www.bibsonomy.org/bibtex/27fe0fabb39a688fd9894e586fe84d415/juraeva},
institution = {Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; The German Cancer Consortium, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Electronic address: c.plass@dkfz.de.},
interhash = {b7907d5f899ff32fa67429d19a74da87},
intrahash = {7fe0fabb39a688fd9894e586fe84d415},
journal = {Cell Rep},
keywords = {ABI-DKFZ},
language = {eng},
medline-pst = {ppublish},
month = aug,
number = 3,
owner = {bbrors},
pages = {798--806},
pmid = {25066126},
timestamp = {2015-06-29T14:34:20.000+0200},
title = {Intratumor DNA methylation heterogeneity reflects clonal evolution in aggressive prostate cancer.},
volume = 8,
year = 2014
}