Clonal Evolution of Glioblastoma Under Therapy  

Oleh:

Jiguang Wang ; Cazzato, Emanuela ; Ladewig, Erik ; Frattini, Veronique ; Rosenbloom, Daniel I. S.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Nature Genetics vol. 48 no. 07 (Jul. 2016), page 768-776.
Topik: CNS Cancer; Personalized Medicine; Transcriptomics

Ketersediaan

Perpustakaan FK Nomor Panggil: N12.K Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

Lihat Detail Induk

Isi artikel

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-ß. Silencing LTBP4 in GBM cells leads to suppression of TGF-ß activity and decreased cell proliferation. In recurrent GBM with wild-type IDH1, high LTBP4 expression is associated with worse prognosis, highlighting the TGF-ß pathway as a potential therapeutic target in GBM.

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