glioblastoma_stem-like_cells

Glioblastoma stem-like cells

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 a multi-centric study, Lazzarini et al. performed genomic and transcriptomics of a large set of patient-derived glioblastoma (GBM) stem-like cells (GSCs).

94 (80 I surgery/14 II surgery) and 53 (42 I surgery/11 II surgery) GSCs lines underwent whole exome and transcriptome analysis, respectively.

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 with 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.

The availability of a large set of fully molecularly characterized Glioblastoma stem-like cells represents a valuable public resource to support the advancement of precision oncology for the glioblastoma treatment 1)


1)
Lazzarini E, Silvestris DA, Benvenuto G, Osti D, Fattore L, Paterra R, Finocchiaro G, Malatesta P, Daga A, Gallotti AL, Galli R, Pelicci G, Tesei A, Bedeschi M, Pallini R, Pasqualini L, Romualdi C, Gallo A, Ricci-Vitiani L, Indraccolo S. Genome-wide profiling of patient-derived glioblastoma stem-like cells reveals recurrent genetic and transcriptomic signatures associated with brain tumors. J Neurooncol. 2023 May 4. doi: 10.1007/s11060-023-04287-6. Epub ahead of print. PMID: 37140883.
  • glioblastoma_stem-like_cells.txt
  • Last modified: 2023/05/04 21:01
  • by administrador