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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Polysome Profiling of a Human Glioblastoma Reveals Intratumoral Heterogeneity

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Author(s):
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Sulla Lupinacci, Fernanda Cristina [1] ; Kuasne, Hellen [1] ; Roffe, Martin [1] ; Vassalakis, Julia Avian [1] ; da Silva, Fernanda Ferreira [1] ; Santos, Tiago Goss [1] ; Andrade, Victor Piana [2] ; Sanematsu, Paulo [3] ; Martins, Vilma Regina [1] ; Rogatto, Silvia Regina [4] ; Maroso Hajj, Glaucia Noeli [1]
Total Authors: 11
Affiliation:
[1] Natl Inst Sci & Technol Oncogenom, AC Camargo Canc Ctr, Int Res Ctr, BR-01509010 Sao Paulo - Brazil
[2] Natl Inst Sci & Technol Oncogenom, Pathol Dept, AC Camargo Canc Ctr, BR-01509010 Sao Paulo - Brazil
[3] Natl Inst Sci & Technol Oncogenom, Neurosurg Dept, AC Camargo Canc Ctr, BR-01509010 Sao Paulo - Brazil
[4] Univ Southern, Inst Reg Hlth Res, Vejle Hosp, DK-5230 Odense - Denmark
Total Affiliations: 4
Document type: Journal article
Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 20, n. 9 MAY 1 2019.
Web of Science Citations: 0
Abstract

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. (AU)

FAPESP's process: 15/15451-3 - Study on the Regulation and Function of the RSK Family in Glioblastomas
Grantee:Martín Roffé
Support type: Regular Research Grants
FAPESP's process: 18/17796-6 - Translationa Control In Cancer - Part II
Grantee:Glaucia Noeli Maroso Hajj
Support type: Regular Research Grants