%0 Journal Article %1 wang2016clonal %A Wang, Jiguang %A Cazzato, Emanuela %A Ladewig, Erik %A Frattini, Veronique %A Rosenbloom, Daniel I S %A Zairis, Sakellarios %A Abate, Francesco %A Liu, Zhaoqi %A Elliott, Oliver %A Shin, Yong-Jae %A Lee, Jin-Ku %A Lee, In-Hee %A Park, Woong-Yang %A Eoli, Marica %A Blumberg, Andrew J %A Lasorella, Anna %A Nam, Do-Hyun %A Finocchiaro, Gaetano %A Iavarone, Antonio %A Rabadan, Raul %D 2016 %I Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. %J Nat Genet %K evolution glioblastoma tcga %N 7 %P 768--776 %T Clonal evolution of glioblastoma under therapy %U http://dx.doi.org/10.1038/ng.3590 %V 48 %X Glioblastoma (GBM) is the most common and aggressive primary brain tumor. To better understand how GBM evolves, we analyzed longitudinal genomic and transcriptomic data from 114 patients. The analysis shows a highly branched evolutionary pattern in which 63% of patients experience expression-based subtype changes. The branching pattern, together with estimates of evolutionary rate, suggests that relapse-associated clones typically existed years before diagnosis. Fifteen percent of tumors present hypermutation at relapse in highly expressed genes, with a clear mutational signature. We find that 11% of recurrence tumors harbor mutations in LTBP4, which encodes a protein binding to TGF-beta. Silencing LTBP4 in GBM cells leads to suppression of TGF-beta activity and decreased cell proliferation. In recurrent GBM with wild-type IDH1, high LTBP4 expression is associated with worse prognosis, highlighting the TGF-beta pathway as a potential therapeutic target in GBM.

@article{wang2016clonal, abstract = {Glioblastoma (GBM) is the most common and aggressive primary brain tumor. To better understand how GBM evolves, we analyzed longitudinal genomic and transcriptomic data from 114 patients. The analysis shows a highly branched evolutionary pattern in which 63% of patients experience expression-based subtype changes. The branching pattern, together with estimates of evolutionary rate, suggests that relapse-associated clones typically existed years before diagnosis. Fifteen percent of tumors present hypermutation at relapse in highly expressed genes, with a clear mutational signature. We find that 11% of recurrence tumors harbor mutations in LTBP4, which encodes a protein binding to TGF-[beta]. Silencing LTBP4 in GBM cells leads to suppression of TGF-[beta] activity and decreased cell proliferation. In recurrent GBM with wild-type IDH1, high LTBP4 expression is associated with worse prognosis, highlighting the TGF-[beta] pathway as a potential therapeutic target in GBM.}, added-at = {2017-05-17T18:54:55.000+0200}, author = {Wang, Jiguang and Cazzato, Emanuela and Ladewig, Erik and Frattini, Veronique and Rosenbloom, Daniel I S and Zairis, Sakellarios and Abate, Francesco and Liu, Zhaoqi and Elliott, Oliver and Shin, Yong-Jae and Lee, Jin-Ku and Lee, In-Hee and Park, Woong-Yang and Eoli, Marica and Blumberg, Andrew J and Lasorella, Anna and Nam, Do-Hyun and Finocchiaro, Gaetano and Iavarone, Antonio and Rabadan, Raul}, biburl = {https://www.bibsonomy.org/bibtex/22bb22fdbc30d0905367755525938f7ae/marcsaric}, description = {Clonal evolution of glioblastoma under therapy : Nature Genetics : Nature Research}, interhash = {f4e72d29672c250157dfb122e085ae65}, intrahash = {2bb22fdbc30d0905367755525938f7ae}, issn = {10614036}, journal = {Nat Genet}, keywords = {evolution glioblastoma tcga}, month = jul, number = 7, pages = {768--776}, publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.}, timestamp = {2017-05-17T18:54:55.000+0200}, title = {Clonal evolution of glioblastoma under therapy}, url = {http://dx.doi.org/10.1038/ng.3590}, volume = 48, year = 2016 }