Tatari, Nazanin, Khan, Shahbaz, Livingstone, Julie, Zhai, Kui, Mckenna, Dillon, Ignatchenko, Vladimir, Chokshi, Chirayu, Gwynne, William D, Singh, Manoj, Revill, Spencer, Mikolajewicz, Nicholas, Zhu, Chenghao, Chan, Jennifer, Hawkins, Cynthia, Lu, Jian-Qiang, Provias, John P, Ask, Kjetil, Morrissy, Sorana, Brown, Samuel, Weiss, Tobias, Weller, Michael, Han, Hong, Greenspoon, Jeffrey N, Moffat, Jason, Venugopal, Chitra, Boutros, Paul C, Singh, Sheila K and Kislinger, Thomas (2022) The proteomic landscape of glioblastoma recurrence reveals novel and targetable immunoregulatory drivers. Acta neuropathologica, 144 (6). pp. 1127-1142. ISSN 1432-0533

Abstract

Glioblastoma (GBM) is characterized by extensive cellular and genetic heterogeneity. Its initial presentation as primary disease (pGBM) has been subject to exhaustive molecular and cellular profiling. By contrast, our understanding of how GBM evolves to evade the selective pressure of therapy is starkly limited. The proteomic landscape of recurrent GBM (rGBM), which is refractory to most treatments used for pGBM, are poorly known. We, therefore, quantified the transcriptome and proteome of 134 patient-derived pGBM and rGBM samples, including 40 matched pGBM-rGBM pairs. GBM subtypes transition from pGBM to rGBM towards a preferentially mesenchymal state at recurrence, consistent with the increasingly invasive nature of rGBM. We identified immune regulatory/suppressive genes as important drivers of rGBM and in particular 2-5-oligoadenylate synthase 2 (OAS2) as an essential gene in recurrent disease. Our data identify a new class of therapeutic targets that emerge from the adaptive response of pGBM to therapy, e

Item Type:	Article
Date Deposited:	28 Dec 2024 00:45
Last Modified:	28 Dec 2024 00:45
URI:	https://oak.novartis.com/id/eprint/56192