Polysome Profiling of a Human Glioblastoma Reveals Intratumoral Heterogeneity

International Journal of Molecular Sciences

TiagoGóss Santos¹  FernandaCristina Sulla Lupinacci¹  FernandaFerreira da Silva¹  Hellen Kuasne¹  GlauciaNoeli Maroso Hajj¹  VilmaRegina Martins¹  JuliaAvian Vassalakis¹  Martin Roffé¹  Paulo Sanematsu²  VictorPiana Andrade³  SilviaRegina Rogatto⁴ 

[1] International Research Center, A.C.Camargo Cancer Center, National Institute of Science and Technology in Oncogenomics, São Paulo 01509-010, Brazil;Neurosurgery Department, A.C.Camargo Cancer Center, National Institute of Science and Technology in Oncogenomics, São Paulo 01509-010, Brazil;Pathology Department, A.C.Camargo Cancer Center, National Institute of Science and Technology in Oncogenomics, São Paulo 01509-010, Brazil;Vejle Hospital, Institute of Regional Health Research, University of Southern, 5230 Odense, Denmark;

关键词: translatome;    glioblastoma;    tumor heterogeneity;    polysome;    mTORC1;    translation control;   

DOI  :  10.3390/ijms20092177

来源: DOAJ

【 摘 要 】

Glioblastoma (GBM) is one of the most aggressive cancers, with median survival of less than 2 years. Despite of considerable advance in molecular classification of GBMs, no improvements in therapy have been described. The scenario is further complicated by tumor heterogeneity and the relationship among genetic, transcriptional and functional findings. Classically, gene expression has been evaluated by steady-state mRNA, however, this does not take translational control into consideration, which contributes considerably to the composition of the proteome. In this study, we evaluated the transcriptomic and translatomic signature of a GBM obtained from a single patient focusing in tumor heterogeneity. In a sampling of eight fragments, we investigated the translation rates, mTORC1 and ERK1/2 pathways and identified both total and polysome associated mRNAs. An increased translation rate was observed in fragments with high-grade histological features. High-grade histology was also associated with the expression of genes related to extracellular matrix (ECM) and angiogenesis, in both transcriptomes and translatomes. However, genes associated with epithelial to mesenchymal transition and stress response, were observed only in translatomes from high-grade fragments. Overall, our results demonstrate that isolation of translated mRNA can be used to identify biomarkers and reveal previously unrecognized determinants of heterogeneity in GBMs.

【 授权许可】

Unknown