Genome-wide profiling of patient-derived glioblastoma stem-like cells reveals recurrent genetic and transcriptomic signatures associated with brain tumors.

Autor: Lazzarini E; Basic and Translational Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, via Gattamelata, 64, 35128, Padova, Italy., Silvestris DA; Unit of Genetics and Epigenetic of Pediatric Cancer, Oncohaematology Department, IRCCS Ospedale Pediatrico Bambino Gesù, Viale di San Paolo 15, 00146, Rome, Italy., Benvenuto G; Department of Biology, University of Padova, Padova, Italy., Osti D; Department of Experimental Oncology, European Institute of Oncology (IEO), IRCCS, 20139, Milan, Italy., Fattore L; SAFU Laboratory, Department of Research, Advanced Diagnostics and Technological Innovation, Translational Research Area, IRCCS Regina Elena National Cancer Institute, Rome, Italy., Paterra R; SC Neurologia 2- Neuroncologia- Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., Finocchiaro G; SC Neurologia 2- Neuroncologia- Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy., Malatesta P; IRCCS Ospedale Policlinico San Martino, Genova, Italy.; Dipartimento di Medicina Sperimentale, Università di Genova, Genova, Italy., Daga A; IRCCS Ospedale Policlinico San Martino, Genova, Italy., Gallotti AL; Neural Stem Cell Biology Unit, Division of Neuroscience, IRCCS San Raffaele Hospital, Via Olgettina 58, Milan, Italy., Galli R; Neural Stem Cell Biology Unit, Division of Neuroscience, IRCCS San Raffaele Hospital, Via Olgettina 58, Milan, Italy., Pelicci G; Department of Experimental Oncology, European Institute of Oncology (IEO), IRCCS, 20139, Milan, Italy.; Department of Translational Medicine, University of Piemonte Orientale, Novara, Italy., Tesei A; Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Bedeschi M; Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) 'Dino Amadori', Meldola, Italy., Pallini R; Department of Neurosurgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del S. Cuore, Largo A. Gemelli, 8, Rome, Italy., Pasqualini L; Basic and Translational Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, via Gattamelata, 64, 35128, Padova, Italy., Romualdi C; Department of Biology, University of Padova, Padova, Italy., Gallo A; Unit of Genetics and Epigenetic of Pediatric Cancer, Oncohaematology Department, IRCCS Ospedale Pediatrico Bambino Gesù, Viale di San Paolo 15, 00146, Rome, Italy. angela.gallo@opbg.net., Ricci-Vitiani L; Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy. lucia.riccivitiani@iss.it., Indraccolo S; Basic and Translational Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS, via Gattamelata, 64, 35128, Padova, Italy. stefano.indraccolo@unipd.it.; Department of Surgery Oncology and Gastroenterology (DiSCOG), University of Padova, Padova, Italy. stefano.indraccolo@unipd.it.
Jazyk: angličtina
Zdroj: Journal of neuro-oncology [J Neurooncol] 2023 May; Vol. 163 (1), pp. 47-59. Date of Electronic Publication: 2023 May 04.
DOI: 10.1007/s11060-023-04287-6
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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