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- Title
Genome-wide profiling of patient-derived glioblastoma stem-like cells reveals recurrent genetic and transcriptomic signatures associated with brain tumors.
- Authors
Lazzarini, Elisabetta; Silvestris, Domenico Alessandro; Benvenuto, Giuseppe; Osti, Daniela; Fattore, Luigi; Paterra, Rosina; Finocchiaro, Gaetano; Malatesta, Paolo; Daga, Antonio; Gallotti, Alberto L.; Galli, Rossella; Pelicci, Giuliana; Tesei, Anna; Bedeschi, Martina; Pallini, Roberto; Pasqualini, Lorenza; Romualdi, Chiara; Gallo, Angela; Ricci-Vitiani, Lucia; Indraccolo, Stefano
- Abstract
Purpose: Patient-derived cancer cell lines can be very useful to investigate genetic as well as epigenetic mechanisms of transformation and to test new drugs. In this multi-centric study, we performed genomic and transcriptomic characterization of a large set of patient-derived glioblastoma (GBM) stem-like cells (GSCs). Methods: 94 (80 I surgery/14 II surgery) and 53 (42 I surgery/11 II surgery) GSCs lines underwent whole exome and trascriptome analysis, respectively. Results: Exome sequencing revealed TP53 as the main mutated gene (41/94 samples, 44%), followed by PTEN (33/94, 35%), RB1 (16/94, 17%) and NF1 (15/94, 16%), among other genes associated to brain tumors. One GSC sample bearing a BRAF p.V600E mutation showed sensitivity in vitro to a BRAF inhibitor. Gene Ontology and Reactome analysis uncovered several biological processes mostly associated to gliogenesis and glial cell differentiation, S − adenosylmethionine metabolic process, mismatch repair and methylation. Comparison of I and II surgery samples disclosed a similar distribution of mutated genes, with an overrepresentation of mutations in mismatch repair, cell cycle, p53 and methylation pathways in I surgery samples, and of mutations in receptor tyrosine kinase and MAPK signaling pathways in II surgery samples. Unsupervised hierarchical clustering of RNA-seq data produced 3 clusters characterized by distinctive sets of up-regulated genes and signaling pathways. Conclusion: The availability of a large set of fully molecularly characterized GCSs represents a valuable public resource to support the advancement of precision oncology for the treatment of GBM.
- Subjects
BRAIN tumors; ONCOLOGY; GLIOBLASTOMA multiforme; TRANSCRIPTOMES; DNA mismatch repair; PROTEIN-tyrosine kinases; HIERARCHICAL clustering (Cluster analysis); INTRACELLULAR calcium
- Publication
Journal of Neuro-Oncology, 2023, Vol 163, Issue 1, p47
- ISSN
0167-594X
- Publication type
Article
- DOI
10.1007/s11060-023-04287-6