Heterogeneity and excitability of BRAFV600E-induced tumors is determined by PI3K/mTOR-signaling state and Trp53-loss

Cases-Cunillera S, van Loo KMJ, Pitsch J, Quatraccioni A, Sivalingam S, Salomoni P, Dietrich D, Schoch S, Becker AJ.

bioRxiv, 2021



Brain tumors with BRAFV600E somatic mutation are diverse.  In this paper the authors determine the molecular factors that determine the brain tumors biology and function.  Brain neoplasms were generated and monitored in vivo for tumor formation.  Neural activity from the acute tumor slices was recorded on Axion's Maestro multielectrode array (MEA) platform.  Finally RNA sequencing was used to analyze the induce neoplasms.

The recorded electrical activity from BRAFV600E-positive/glioneuronal tumors slices were epileptogenic and showed altered neuronal activity within the tumor microenvironment.  The extracellular electrical activity recorded in the MEA well could be classified based on three different categories:

  • tumor core - showed the lowest frequency of spontaneous activity
  • tumor border 
  • non-fluorescent tissue (pre-existing brain tissue)

Brain slices have levels of neuronal activity lower than in vivo recordings.  The authors, changed the media to one that would favor network activity.   While the activity in the tumor did not change, the activity in the transitional zone increased.