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PDGF gene expression and p53 alterations contribute to the biology of diffuse astrocytic gliomas by Mehul Kumar; Mathieu Meode; Michael Blough; Gregory Cairncross; Pinaki Bose is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is PDGF gene expression and p53 alterations contribute to the biology of diffuse astrocytic gliomas about?

## Abstract Diffuse, histologically lower grade astrocytomas of adults (LGAs) are classified based on the mutational status of the isocitrate dehydrogenase (IDH) genes. While wild-type (WT) LGAs often evolve quickly to glioblastoma (GBM), mutant tumors typically follow an indolent course. To find possible effectors of these different behaviors, we compared their respective transcriptomes. Unlike mutant LGAs, platelet-derived growth factor (PDGF) signaling was significantly enriched in WT tumors, and PDGFA was the top overexpressed gene in the pathway. Moreover, methylation of the PDGFA and PDGFD promoters emerged as a possible mechanism for their low expression in mutant tumors. Copy number gain of chromosome 7 co-occurred with high expression of PDGFA in WT cases, and high expression of PDGFA was associated with aneuploidy, extracellular matrix (ECM)-related immunosuppressive features and poor prognosis. We also noted that high PDGFA expression in WT cases occurred irrespective of tumor grade and that multiple mechanisms of p53 pathway inactivation accompanied progression to GBM in PDGFA-overexpressing tumors. Conversely, TP53 point mutations were an early and constant feature of

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Author

Mehul Kumar; Mathieu Meode; Michael Blough; Gregory Cairncross; Pinaki Bose

Publisher

Springer Science and Business Media LLC

Published

2023

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)