Data from The Transcriptional Regulatory Network of Proneural Glioma Determines the Genetic Alterations Selected during Tumor Progression
Year: 2023
Type: other
Abstract: Proneural glioblastoma is defined by an expression pattern resembling that of oligodendrocyte progenitor cells and carries a distinctive set of genetic alterations. Whether there is a functional relationship between the proneural phenotype and the associated genetic alterations is unknown. To evaluate this possible relationship, we performed a longitudinal molecular characterization of tumor progression in a mouse model of proneural glioma. In this setting, the tumors acquired remarkably consistent genetic deletions at late stages of progression, similar to those deleted in human proneural glioblastoma. Further investigations revealed that p53 is a master regulator of the transcriptional network underlying the proneural phenotype. This p53-centric transcriptional network and its associated phenotype were observed at both the early and late stages of progression, and preceded the proneural-specific deletions. Remarkably, deletion of p53 at the time of tumor initiation obviated the acquisition of later deletions, establishing a link between the proneural transcriptional network and the subtype-specific deletions selected during glioma progression. Cancer Res; 74(5); 1440–51. ©2014 AACR.
Authors: Adam M. Sonabend, Mukesh Bansal, Paolo Guarnieri, Liang Lei, Benjamin Amendolara, Craig Soderquist, Richard Leung, Jonathan Yun, Benjamin Kennedy, Julia Sisti, Samuel Bruce, Rachel Bruce, Reena Shakya, Thomas Ludwig, Steven Rosenfeld, Peter A. Sims, Jeffrey N. Bruce, Andrea Califano, Peter Canoll
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4361824463