Our integrative analysis of PBTA host-tumor genomes has been published in Nature Communications!

We’re thrilled to share the publication of our latest study, “Germline pathogenic variation impacts somatic alterations and patient outcomes in pediatric central nervous system tumors,” now out in Nature Communications. Led by Dr. Ryan Corbett] in the Rokita Lab, this work represents a comprehensive multi-omic analysis of germline and somatic data from 830 pediatric brain tumor patients in the #PBTA — truly a tour de force by the team.

We highlight the importance of germline testing at diagnosis, identifying rare germline pathogenic (P) or likely pathogenic (LP) variants in 48 patients (5.7%) who had no clinically reported cancer predisposition syndrome. Among all P/LP carriers, 34.6% had putative somatic second hits or loss-of-function tumor alterations, consistent with classical tumor suppressor models. We link germline P/LP variation with somatic events, tumor histologies, molecular subtypes, and clinical outcomes — with some variants associated with protection and others with poorer survival. Together, these findings deepen our understanding of how inherited or early-life genetic changes shape pediatric CNS tumor development, behavior, and outcomes. They pave the way for improved diagnosis, risk stratification, monitoring, and targeted therapy.

🙏 Enormous thanks to our collaborators Children’s Hospital of Philadelphia — especially my partner-in-crime Sharon Diskin and co-first author Rebecca Kaufman. Thank you to our clinical experts whose insights into gene lists and variant curation were invaluable: Miriam Bornhorst, Suzanne MacFarland, Kristina Cole, and Shelly McQuaid.

Special thanks to the patients and families, the Children’s Brain Tumor Network for creating this dataset, the anonymous donors to the Brain Tumor Institute, Gabriella Miller Kids First Data Resource Center for supporting us with cloud credits, and every member of the team whose dedication made this possible.

Read the Children’s National press release here.