TY - JOUR
T1 - Intratumor DNA methylation heterogeneity reflects clonal evolution in aggressive prostate cancer
AU - Brocks, David
AU - Assenov, Yassen
AU - Minner, Sarah
AU - Bogatyrova, Olga
AU - Simon, Ronald
AU - Koop, Christina
AU - Oakes, Christopher
AU - Zucknick, Manuela
AU - Lipka, Daniel Bernhard
AU - Weischenfeldt, Joachim
AU - Feuerbach, Lars
AU - Lari, Richard Cowper-Sal
AU - Lupien, Mathieu
AU - Brors, Benedikt
AU - Korbel, Jan
AU - Schlomm, Thorsten
AU - Tanay, Amos
AU - Sauter, Guido
AU - Gerhaeuser, Clarissa
AU - Plass, Christoph
N1 - Publisher Copyright: © 2014 The Authors.
PY - 2014/8/7
Y1 - 2014/8/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84924627714&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.celrep.2014.06.053
DO - https://doi.org/10.1016/j.celrep.2014.06.053
M3 - مقالة
SN - 2211-1247
VL - 8
SP - 798
EP - 806
JO - Cell Reports
JF - Cell Reports
IS - 3
ER -