Nicholas Nuechterlein, Allison Shelbourn, Frank Szulzewsky, Sonali Arora, Michelle Casad, Siobhan Pattwell, Leyre Merino-Galan, Erik Sulman, Sumaita Arowa, Neriah Alvinez, Miyeon Jung, Desmond Brown, Kayen Tang, Sadhana Jackson, Stefan Stoica, Prashant Chittaboina, Yeshavanth K Banasavadi-Siddegowda, Hans-Georg Wirsching, Nephi Stella, Linda Shapiro, Patrick Paddison, Anoop P Patel, Mark R Gilbert, Zied Abdullaev, Kenneth Aldape, Drew Pratt, Eric C Holland, Patrick J Cimino
Glioblastoma is universally fatal and characterized by frequent chromosomal copy number alterations harboring oncogenes and tumor suppressors. In this study, we analyzed exome-wide human glioblastoma copy number data and found that cytoband 6q27 is an independent poor prognostic marker in multiple data sets. We then combined CRISPR-Cas9 data, human spatial transcriptomic data, and human and mouse RNA sequencing data to nominate PDE10A as a potential haploinsufficient tumor suppressor in the 6q27 region. Mouse glioblastoma modeling using the RCAS/tv-a system confirmed that Pde10a suppression induced an aggressive glioma phenotype in vivo and resistance to temozolomide and radiation therapy in vitro...
April 8, 2024: Genes & Development