Microarray Analysis Of Polysome-Associated Mrnas From Different Regions Of The Same Human Glioblastoma Reveals Intratumoral Heterogeneity

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LAGlioblastoma is among the most aggressive tumor type and less responsive to chemotherapeutic agents, thus a better understanding of the behavior of these tumors 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. The identification of mRNAs target of translational alterations in tumors can show gene expression profiles that better reflect the population of proteins. In this work we were able to identify mRNAs differentially translated in a human glioblastoma that presented histologically different parts. The sample was divided in 8 pieces that were classified as high or low grade based on histological characteristics. Actively translating ribosomes and their associated mRNAs were isolated biochemically through a polysomal profile. Total and polysomal mRNA was then extracted and submitted to a microarray analysis. By comparing high vs low grade tumor pieces, we were able to identify more differentially translated genes (138 genes) than differentially expressed genes (43 genes). Among the differentially translated mRNAs, there are many related to proliferation, development and cancer. By Integrated Pathway Analysis, we identified the TGF-β pathway among the the most relevant for grade progression. Thus, the technique of isolating mRNAs engaged in translation can be used to identify biomarkers of tumor progression, leading to new therapeutic approaches.Citation Format: Glaucia N. Hajj, Fernanda S. Lupinacci, Martin Roffe, Hellen Kuasne, Tiago G. Santos, Victor P. Andrade, Paulo Sanematsu, Vilma R. Martins, Silvia R. Rogatto. Microarray analysis of polysome-associated mRNAs from different regions of the same human glioblastoma reveals intratumoral heterogeneity. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2389.