Transcriptome-Wide Analysis of Brain Cancer Initiated by Polarity Disruption in Drosophila Type II Neuroblasts

TL;DR

This study uses fruit flies to model brain cancer by disrupting cell polarity in specific neural stem cells, revealing insights into human glioblastoma.

Contribution

The study introduces a Drosophila model with polarity disruption in type II neuroblasts to better understand human brain tumor origins.

Findings

Disrupting polarity in Drosophila type II neuroblasts leads to malignant masses resembling human GBM.

Transcriptome analysis shows significant overlap between the model and human primary GBMs.

The model captures key molecular features of human brain tumorigenesis.

Abstract

Brain tumors, in particular gliomas and glioblastoma multiforme (GBM), are thought to originate from different cells facing specific founding insults, a feature that partly justifies the complexity and heterogeneity of these severe forms of cancer. However, gliomas and GBM are usually reproduced in animal models by inducing molecular alterations in mature glial cells, which, though being part of the puzzle, do not represent the whole picture. To fill this conceptual gap, we previously developed a neurogenic model of brain cancer in Drosophila, demonstrating that the loss of cell polarity in neural stem cells (called neuroblasts in the fruit fly) is sufficient to promote the formation of malignant masses that continue to grow in the adult, displaying several phenotypic traits typical of human GBM. Here, we expand on previous work by restricting polarity disruption to Drosophila type II neuroblasts, whose self-renewal is comparable to that of mammalian neural progenitors, with the aim to capture the molecular signature of the resulting cancers in a specific and reproducible context. A comparison of the most deregulated transcripts with those found in human primary GBMs confirmed that our model can be proficiently used to delve into the roots of human brain tumorigenesis.

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