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Characterizing TP53 and PPM1D Mutations as Resistance Drivers to Radiation Therapy in Diffuse Intrinsic Pontine Gliomas
dbGaP
Data Resource:  dbGaP
Point of Contact:  
Rameen Beroukhim, MD, PhD,  
Project

About This Dataset
Pediatric high-grade gliomas (pHGGs), encompassing diffuse midline gliomas (DMGs) and hemispheric tumors, represent the most common cause of cancer-related deaths in children age 0-14 years. Over the last decade, several landmark papers have revealed recurrent single nucleotide variants (SNVs) in the core histones H3.3 and H3.1, co-occurring with alterations in the TP53 signaling pathway and receptor tyrosine kinases (RTKs). However, the contribution of structural variants (SVs) to gliomagenesis has not been systematically explored. We performed a comprehensive analysis of whole genome sequencing (WGS) data on pediatric high-grade gliomas (pHGGs) from 179 children, including 61 hemispheric tumors and 118 diffuse midline gliomas, or DMGs, of which 61 are novel to this study. Among the DMGs, 84 (71%) were from pre-treatment biopsies including 33 obtained from the first multi-institutional North American clinical trial to incorporate diagnostic biopsies. This represents the largest cohort of pretreatment DMGs with whole genome sequencing to date. This large cohort of whole genome sequences provides an unparalleled opportunity to assess significantly recurrent structural variants in pHGG and their associations with driver SNVs and SCNAs.
Core Data Elements
Number of Cases
61
Case Sex
Female (38); Male (23)
Case Age At Diagnosis
0 to 4 years (12); 5 to 9 years (28); 10 to 14 years (15); 15 to 19 years (5); Pediatric and Young Adult (<40 years) (1)
Case Race
Black or African American (3); White (14); Not Reported (6); Unknown (38)
Case Ethnicity
Not Reported (61)
Case Disease Diagnosis
Pediatric High-Grade Glioma (61)
Case Tumor Site
Hemispheric (18); Midline (43)
Number of Samples
122
Sample Anatomic Site
Blood (61); Brain (61)
Sample Is Normal
Yes (61); No (61)
Additional Data Elements
CLINICAL TRIAL IDENTIFIER
DBGAP STUDY IDENTIFIER
GEO STUDY IDENTIFIER
Grant Information
5R01CA219943
Characterizing TP53 and PPM1D mutations as resistance drivers to radiation therapy in Diffuse Intrinsic Pontine Gliomas
Published In
https://doi.org/10.1038/s43018-022-00403-z
Charts
Female (38); Male (23)
38Female