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000119711 0247_ $$2doi$$a10.1016/j.celrep.2014.06.053
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000119711 1001_ $$0P:(DE-He78)3860e24c3868c15255c3383a58e8d5b8$$aBrocks, David$$b0$$eFirst author$$udkfz
000119711 245__ $$aIntratumor DNA methylation heterogeneity reflects clonal evolution in aggressive prostate cancer.080
000119711 260__ $$aMaryland Heights, MO$$bCell Press$$c2014
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000119711 520__ $$aDespite 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.
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000119711 7001_ $$0P:(DE-He78)45a6854ecf41ba2e65ca3ba0d560f14c$$aAssenov, Yassen$$b1$$udkfz
000119711 7001_ $$aMinner, Sarah$$b2
000119711 7001_ $$0P:(DE-He78)3493620cedb8f0b17c9e1b424c0e21db$$aBogatyrova, Olga$$b3$$udkfz
000119711 7001_ $$aSimon, Ronald$$b4
000119711 7001_ $$aKoop, Christina$$b5
000119711 7001_ $$0P:(DE-HGF)0$$aOakes, Christopher$$b6
000119711 7001_ $$0P:(DE-HGF)0$$aZucknick, Manuela$$b7
000119711 7001_ $$0P:(DE-He78)c403a040c97f91902a7d31b93859f9fc$$aLipka, Daniel$$b8$$udkfz
000119711 7001_ $$aWeischenfeldt, Joachim$$b9
000119711 7001_ $$0P:(DE-He78)75e2afb3ea0812786cc551c10679b67d$$aFeuerbach, Lars$$b10$$udkfz
000119711 7001_ $$aCowper-Sal Lari, Richard$$b11
000119711 7001_ $$aLupien, Mathieu$$b12
000119711 7001_ $$0P:(DE-He78)fc949170377b58098e46141d95c72661$$aBrors, Benedikt$$b13$$udkfz
000119711 7001_ $$aKorbel, Jan$$b14
000119711 7001_ $$aSchlomm, Thorsten$$b15
000119711 7001_ $$aTanay, Amos$$b16
000119711 7001_ $$aSauter, Guido$$b17
000119711 7001_ $$0P:(DE-He78)3c4679d03b730156fae20c4948722efe$$aGerhäuser, Clarissa$$b18$$udkfz
000119711 7001_ $$0P:(DE-He78)4301875630bc997edf491c694ae1f8a9$$aPlass, Christoph$$b19$$eLast author$$udkfz
000119711 7001_ $$0P:(DE-HGF)0$$aProject, ICGC Early Onset Prostate Cancer$$b20$$eLast author
000119711 773__ $$0PERI:(DE-600)2649101-1$$a10.1016/j.celrep.2014.06.053$$gVol. 8, no. 3, p. 798 - 806$$n3$$p798 - 806$$tCell reports$$v8$$x2211-1247$$y2014
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