TY  - JOUR
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
AU  - Weischenfeldt, Joachim
AU  - Feuerbach, Lars
AU  - Cowper-Sal Lari, Richard
AU  - Lupien, Mathieu
AU  - Brors, Benedikt
AU  - Korbel, Jan
AU  - Schlomm, Thorsten
AU  - Tanay, Amos
AU  - Sauter, Guido
AU  - Gerhäuser, Clarissa
AU  - Plass, Christoph
AU  - Project, ICGC Early Onset Prostate Cancer
TI  - Intratumor DNA methylation heterogeneity reflects clonal evolution in aggressive prostate cancer.080
JO  - Cell reports
VL  - 8
IS  - 3
SN  - 2211-1247
CY  - Maryland Heights, MO
PB  - Cell Press
M1  - DKFZ-2017-00338
SP  - 798 - 806
PY  - 2014
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.
LB  - PUB:(DE-HGF)16
C6  - pmid:25066126
DO  - DOI:10.1016/j.celrep.2014.06.053
UR  - https://inrepo02.dkfz.de/record/119711
ER  -