Evolutionary history of deadly brain tumor
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Glioblastoma (GBM) is the most common and most aggressive brain tumor in adults. Current treatment involves surgery, radiotherapy, and chemotherapy plus alkylation agents. Although intensively treated, GBM will always recur. The recurrent tumor will be typically resistant to therapy, leading to death. To understand how GBM evolves under therapy, we have analyzed longitudinal genomic/transcriptomic data from 114 patients, and uncovered the evolutionary landscape of GBM. Importantly, we found 63% of patients experience expression-based subtype changes, 15% of tumors present hypermutation at relapse in highly expressed genes, and 11% of recurrence tumors harbor mutations in LTBP4, which encodes a protein binding to TGF-β.
“Clonal evolution of glioblastoma under therapy”
AUTHORS: Jiguang Wang, Emanuela Cazzato, Erik Ladewig, Veronique Frattini, Daniel I S Rosenbloom, Sakellarios Zairis, Francesco Abate, Zhaoqi Liu, Oliver Elliott, Yong-Jae Shin, Jin-Ku Lee, In-Hee Lee, Woong-Yang Park, Marica Eoli, Andrew J Blumberg, Anna Lasorella, Do-Hyun Nam, Gaetano Finocchiaro, Antonio Iavarone, Raul Rabadan.
LINK TO PUBLICATION:
Nature Genetics 2016 June 6. doi: 10.1038/ng.3590.