DIPGs are especially lethal and confer a despairingly short 11-month median survival due to their aggressive phenotype and lack of therapeutic options. Molecular characterization of pediatric brain tumors is stimulating the development and testing of targeted therapies for precision medicine. However, effective targeted options are still unavailable for DIPG.
In our initial cohort of sequencing high-risk brain tumors, we found that over 20% of pHGG harbor fusions, a rate higher than larger datasets published by other groups. As seen in other solid tumors and human cancers, in-frame fusions involving established tumor drivers are frequently pivotal clonal events that are essential to tumor survival and growth. Our collaborative team (Cieslik lab) includes a bioinformatics group that specializes in the optimization of RNA-seq analysis and fusion calling. The CODAC pipeline has transformed the fusion landscape and therapeutic options for adult solid tumors using a novel in house pipeline that had proven effective for advancing oncogenic fusion calling beyond other established tools in use. In this proposal, we will compare CODAC to multiple other fusion-calling tools on two independent datasets of DIPG RNA-seq data, and then perform validation of targeting of CODAC-called fusions in human and mice models
What are the goals of this project?
The goals of this project are to determine the transformability of unique CODAC-called fusions in DIPG model and to determine the targetability of unique CODAC-called fusions in DIPG models
What is the impact of this project?
Children with DIPG are in great need of harnessing the successes seen in precision medicine in other solid tumors. This proposal will lead to clarification of key computational features to be employed in performing RNA-seq on DIPG tissue. We are optimistic this will lead to an optimized platform for the identification of novel targets for this deadly disease
Why the CBTN request is important to this project?
The CBTN has aggregated RNA-seq data from approximately 100 DIPG samples which it will share along with de-identified clinical data with our investigative team. We will perform fusion calling and comparison on the CBTN data using multiple fusion pipelines
The Children's Brain Tumor Network contributed to this project by providing access to the Pediatric Brain Tumor Atlas.
Marcin Cieslik, bioinformatician
Carl Koschmann, MD
Dr. Koschmann is a Pediatric Neuro-Oncologist in the Department of Pediatrics and a Principal Investigator of an independent translational Pediatric Neuro-Oncology laboratory. His work in the clinic and lab complement and drive each other, resulting in a clear goal to improve therapies for childr
Michigan Medicine C.S. Mott Children’s Hospital
Brainstem glioma- Diffuse intrinsic pontine glioma
A presumptive diagnosis of DIPG based on classic imaging features, in the absence of a histologic diagnosis, has been routinely employed. Increasingly however, histologic confirmation is obtained for both entry into research studies and molecular characterization of the tumor.[