Glioblastoma multiforme (GBM) is the most malignant
brain tumor with patient mortality rate close to 100%, 5-yr survival rate of ∼5%, and a median survival of 14 mo. GBMs have notorious histomorphologic and molecular heterogeneities thus giving hope for development of future personalized
therapies. We describe here a case of a 48-yr-old male patient with three-nodular GBM. To address the question of intratumoral molecular heterogeneity, a comparative analysis of gene expression was performed by using multiple samples collected from different
tumor sites with the aid of intraoperative magnetic resonance imaging (MRI). Sixteen GBM biosamples from parietal, temporal, and temporo-polar localizations were collected from primary, recurrent, and second recurrent
tumors and were obtained and investigated by
RNA sequencing. Our investigations revealed that biosamples derived from different
tumor sites differ in their gene expression profiles with classical or mesenchymal signatures associated with clinically distinct molecular subtypes of GBM found within the same
tumor. The results also showed significant differences in the expression of genes specific for targeted
therapeutics. Our investigations have enabled the identification of four novel fusion transcripts-KIF5C-NTRK3, AC016907.2-ALK, CNTNAP3-NTRK2, and ZNF135-FGFR2-each present in only one sample. We found no differences between untreated and recurrent stages in the expression levels of genes involved in fusion transcripts, suggesting the lack of association between fusion transcript and treatment response. In contrast, longitudinal changes in the expression of
VEGF and MGMT genes were concordant with the
tumor response to
bevacizumab and
temozolomide. Our study underscores the importance of integrating a multisampling approach and
RNA sequencing and demonstrates the predictive merit of an integrated approach for differentiating genomic aberrations associated with untreated or post-treatment recurrent GBMs.