Translatomic applied to the discovery of molecular alterations in gliomas

Abstract

Glioblastoma multiforme (GBM) is among the most aggressive tumor types and less responsive to chemotherapeutic agents, thus a better understanding of the behavior of these tumor types may help to develop new treatments for this disease. Currently, many genome-wide projects attempt to define general patterns of gene expression based on deep sequencing or microarray data from total mRNA populations. However, this approach provides little information about the molecular mediators of tumor biology, because the expression levels of mRNAs do not necessarily reflect the levels of proteins. On the other hand, the identification of mRNAs target of translational alterations in tumors can show gene expression profiles that had better reflect the population of proteins. Thus, in this project we intend to deploy the technique of isolating mRNAs associated with polysomes (actively engaged in translation) with next-generation sequencing, currently called translatomics. These results will allow us to define not only gene expression profiles that correlate with tumor characteristics, but also guide the discovery of proteins with altered expression which could be important mediators of tumor processes. The use of this technique in human glial tumor samples from the Hospital AC Camargo Biobank has the potential to be a powerful tool applied to the clinic, leading to the development of targeted therapeutic approaches. (AU)