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Clonal Evolution of Glioblastoma under Therapy

Identifiers: SRA: SRP074425
BioProject: PRJNA320312
Study Type: 
Abstract: Glioblastoma (GBM) constitutes the most common and aggressive primary brain tumor. To better understand how GBM evolves we analyzed longitudinal genomic and transcriptomic data of 114 patients. The analysis reveals a highly branched evolutionary pattern in which 63% of patients experience expression-based subtype changes. The branching pattern together with estimates of evolutionary rates suggest that the relapse associated clone typically preexisted years before diagnosis. 15% of tumors present hypermutations at relapse in highly expressed genes with a clear mutational signature. We find that 11% of recurrent tumors harbor mutations in LTBP4, a protein binding to TGF-ß. Silencing LTBP4 in GBM cells leads to TGF-ß activity suppression and decreased proliferation. In IDH1-wild-type recurrent GBM, high LTBP4 expression is associated with worse prognosis, highlighting the TGF-ß pathway as a potential therapeutic target in GBM.

Related SRA data

83 ( 83 samples )
83 (1.0Tbp; 463.2Gb)
Additional objects:
File type count
bam 83