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Estibaliz Lopez-Rodrigo

Backer

Ludwig Institute for Cancer Research and Parker Institute for Cancer Immunotherapy

About this

Project

Pediatric Low Grade Gliomas (PLGG) are the most common brain tumor in children. BRAFV600E is found in up to 20% of PLGG cases and is associated to a worse prognosis with a 75% risk of relapse and progression. Relapse, progression and Malignant transformation (MT) into secondary High Grade Glioma (sHGG) has poor prognosis. In the majority of cases, factors leading to progression and MT are unknown. Somatic mutations in Neural Stem Cell (NSC) progenitors during development lead to the development of PLGG. There is growing evidence of the existence of somatic mutations in human non-tumoral tissues, including driver ‘cancer’ mutations, that can affect cellular fitness, and their association to developmental and inflammatory diseases.

We hypothesize that somatic mosaic complementation between mutations in NSC progenitors and mutations in the microenvironment during development can influence glioma phenotype.

Ask The

Scientists

Ask the scientists

What are the goals of this project?

We will characterize the presence, nature, frequency, and functional consequences of microglial genomic mosaicism in human pediatric low grade and high grade glioma patients

What is the impact of this project?

Early detection of mosaic mutations in the tumor microenvironment could inform of risk of progression, helping stratify patients and design therapeutic interventions ultimately improving pediatric glioma patient outcomes. Furthermore, our results could reveal complementary somatic mosaicism as a novel driver of tumorigenesis not only in pediatric glioma, but possibly in other developmental tumors, which is a novel concept that has not been explored.

Why the CBTN request is important to this project?

Our proof-of-concept studies in mice, strongly suggest that the presence of somatic mutations in the tumor microenvironment, in our case microglia, contribute to tumor grade. Therefore, we want to test this novel hypothesis in human samples. Since our model is recapitulating a developmental disease, we want to focus on the analysis of samples from pediatric patients, therefore the contribution of a pediatric brain tumor tissue bank is of utmost importance. Obtaining samples from the CBTTC, especially from HGG patients, will allow us to increase the sensitivity of our study.

Specimen Data

The Children's Brain Tumor Network will contribute to this project by providing tumor tissue and peripheral blood mononuclear cells.