Abstract 1120: Glioblastoma whole transcriptome analysis: molecular mechanisms related to recurrence-free survival (RFS)
Authors: Franceschi Sara , Lessi Francesca , Aretini Paolo , Carbone Francesco G. , Scatena Cristian , La Ferla Marco , Ortenzi Valerio , Vannozzi Riccardo , Bevilacqua Generoso , Naccarato Antonio G. , Mazzanti Chiara M. 
Published: August 2015

Introduction. Diffusely infiltrating astrocytomas represent the most frequent intracranial neoplasms, with the glioblastoma (GB) as the most malignant phenotypic endpoint. Surgical resection, radiotherapy and adjuvant chemotherapy currently represent the standard of care for this disease. From a practical perspective, controlling growth and spreading of the recurrence may have a great impact on disease-free survival. The invasive nature of glioblastoma cells represents a major cause of therapeutic failure, so clarification of the molecular mechanisms associated with cellular migration and invasion is crucial to allow better prediction of these patient. Our study had the intent to provide novel information on glioblastoma behavior, with regard to the type of genetic changes involved in length of recurrence free survival time.

Materials and Methods. We used whole-transcriptome RNA sequencing (Ion Proton system) to analyze 12 primary formalin fixed, paraffin embedded GBs specifically selected for different length of time of first recurrence.

Results. A total of 83 genes resulted to have a statistical significant differential expression, which allowed us to distinguish three distinct groups of tumors with different recurrence free survival times: the short term group (S) with recurrence free survival time less than 6 months (n = 6), the medium group (M) between 16 and 23 months (n = 3), and the long term group (L) with more than 25 months (n = 3). Gene expression comparison analysis identified 51, 21, 26 significant genes between L/S, L/M and S/M respectively. Interestingly the highest number of genes differentialy expressed was found between the two extreme groups (S vs L). Two genes, BOD1L1 and GLUD2 were identified as significantly upregulated in the L group.

Conclusions. The analysis of the whole transcriptome of GBs, with different recurrence free survival time, revealed that many of the genes that seem to be related to time of recurrence, after first surgery, are involved in the epigenetic landscape of the transcriptional potential of the cell such as histone and miRNA expression dis-regulation. Two genes were confirmed such as BOD1L1, which is mostly unknown and seems to be involved in the bio-orientation of chromosomes, and the mitochondrial enzyme GLUD2 which has been recently reported as involved in glioma growth. Moreover, some of the upregulated genes, in the group with the worst prognosis, had been related to the Rho family of GTPases which are key mediators of GB invasion. More thorough analyses are ongoing. A comprehensive better understanding of the molecular mechanisms underlying GB recurrence free survival would make a long step forward in the improvement of the clinical management of patients with such deadly disease.

Citation Format: Sara Franceschi, Francesca Lessi, Paolo Aretini, Francesco G. Carbone, Cristian Scatena, Marco La Ferla, Valerio Ortenzi, Riccardo Vannozzi, Generoso Bevilacqua, Antonio G. Naccarato, Chiara M. Mazzanti. Glioblastoma whole transcriptome analysis: molecular mechanisms related to recurrence-free survival (RFS). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1120. doi:10.1158/1538-7445.AM2015-1120