PPM1D mutations silence NAPRT gene expression and confer NAMPT inhibitor sensitivity in glioma

• Published in: Nature communications Vol. 10; no. 1; pp. 3790 - 10
• Main Authors: Fons, Nathan R., Sundaram, Ranjini K., Breuer, Gregory A., Peng, Sen, McLean, Ryan L., Kalathil, Aravind N., Schmidt, Mark S., Carvalho, Diana M., Mackay, Alan, Jones, Chris, Carcaboso, Ángel M., Nazarian, Javad, Berens, Michael E., Brenner, Charles, Bindra, Ranjit S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.08.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 38/109; 38/15; 38/77; 45/23; 45/41; 45/70; 59/5; 631/67/1922; 631/67/395; 631/67/68/2486; 96/1; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Astrocytes; Biosynthesis; Brain Stem Neoplasms - drug therapy; Brain Stem Neoplasms - genetics; Brain Stem Neoplasms - pathology; Brain tumors; Cell Line, Tumor; Child; Children; CpG islands; Cytokines - antagonists & inhibitors; Diffuse Intrinsic Pontine Glioma - drug therapy; Diffuse Intrinsic Pontine Glioma - genetics; Diffuse Intrinsic Pontine Glioma - pathology; DNA Methylation; Epigenetic Repression; Female; Gene expression; Gene Expression Regulation, Neoplastic; Genomes; Glioma; Humanities and Social Sciences; Humans; Inhibitors; Mice; multidisciplinary; Mutation; NAD; Nicotinamide; Nicotinamide phosphoribosyltransferase; Nicotinamide Phosphoribosyltransferase - antagonists & inhibitors; Nicotinamide Phosphoribosyltransferase - genetics; Nicotinamide Phosphoribosyltransferase - metabolism; Nicotinic acid; Pediatrics; Phosphoribosyltransferase; Pons - cytology; Pons - pathology; Primary Cell Culture; Protein phosphatase; Protein Phosphatase 2C - genetics; Protein Phosphatase 2C - metabolism; Science; Science (multidisciplinary); Synthetic Lethal Mutations; Tumors; Xenograft Model Antitumor Assays

Pediatric high-grade gliomas are among the deadliest of childhood cancers due to limited knowledge of early driving events in their gliomagenesis and the lack of effective therapies available. In this study, we investigate the oncogenic role of PPM1D, a protein phosphatase often found truncated in p...