Clonal variation in drug and radiation response among glioma-initiating cells is linked to proneural-mesenchymal transition (HTA 2.0)

Intra-tumor heterogeneity is a hallmark of glioblastoma multiforme, and thought to negatively affect treatment efficacy. Here we establish libraries of glioma-initiating cell (GIC) clones from patient samples and find extensive molecular and phenotypic variability between clones, including a wide range of responses to radiation and drugs. This widespread variability was observed as a continuum of multitherapy resistance phenotypes linked to a proneural-to-mesenchymal shift in the transcriptome.

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Segerman A, Niklasson M, Haglund C, Bergström T, Jarvius M, Xie Y, Westermark A, Sönmez D, Hermansson A, Kastemar M, Naimaie-Ali Z, Nyberg F, Berglund M, Sundström M, Hesselager G, Uhrbom L, Gustafsson M, Larsson R, Fryknäs M, Segerman B, Westermark B