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Ana Guerreiro Stücklin

University Children's Hospital Zürich
Zürich, Switzerland



Swiss National Science Foundation

About this


Oncogenic fusions involving receptor tyrosine kinases (RTK) drive a group of low- and high-grade gliomas (LGG and HGG) in young children. The most common RTK rearrangements involve the oncogenes ALK/ROS1/NTRK/MET and provide an excellent opportunity for therapeutic targeting. These alterations are similar to those observed in multiple unrelated adult and pediatric tumor types, but their roles in gliomagenesis are still largely unknown.

The clinical features and natural history of pediatric RTK-driven gliomas remains uncharacterized. They are more common in infants but also prevalent in older children and adolescents. Interestingly, similar oncofusions drive both benign and malignant gliomas and additional genetic/epigenetic factors are likely to play a role in tumor behavior and explain the clinical heterogeneity.

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What are the goals of this project?

In this project, we seek to characterize the genetic, epigenetic and transcriptional landscape of RTK-driven pediatric LGG and HGG. To define clinically-relevant tumor subgroups and assess their prognostic significance, we will evaluate the correlation between molecular and clinical characteristics.

In a first step, we will analyze WGS, WES and RNAseq raw and processed data of gliomas (all grades) already generated by the Children's Brain Tumor Network. Integration of clinical data – including age, histology, tumor location, dissemination, time to progression(s) and overall survival - will allow us to identify the molecular characteristics that dictate clinical presentation and determine benign vs malignant behavior.

In a second step, we intend to expand the cohort and profile additional samples available through CBTN (a detailed separate request will be made for specimen access). Lastly, based on the mechanistic insights gained, we will design and validate new drug combination strategies to accelerate clinical translation.

What is the impact of this project?

Taken together, these studies will provide mechanistic insights into RTK-fused gliomas and enable precision medicine approaches to treat these tumors.