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

被引：3

作者：

Lazzarini, Elisabetta ^{[1
]}

Silvestris, Domenico Alessandro ^{[2
]}

Benvenuto, Giuseppe ^{[3
]}

Osti, Daniela ^{[4
]}

Fattore, Luigi ^{[5
]}

Paterra, Rosina ^{[6
]}

Finocchiaro, Gaetano ^{[6
]}

Malatesta, Paolo ^{[7
,8
]}

Daga, Antonio ^{[7
]}

Gallotti, Alberto L. ^{[9
]}

Galli, Rossella ^{[9
,12
]}

Pelicci, Giuliana ^{[4
,10
]}

Tesei, Anna ^{[11
]}

Bedeschi, Martina ^{[11
]}

Pallini, Roberto

Pasqualini, Lorenza ^{[1
]}

Romualdi, Chiara ^{[3
]}

Gallo, Angela ^{[2
]}

Ricci-Vitiani, Lucia ^{[13
]}

Indraccolo, Stefano ^{[1
,14
]}

机构：

[1] Ist Oncol Veneto IOV IRCCS, Basic & Translat Oncol Unit, Via Gattamelata 64, I-35128 Padua, Italy

[2] IRCCS Osped Pediatr Bambino Gesu, Oncohaematol Dept, Unit Genet & Epigenet Pediat Canc, Viale San Paolo 15, I-00146 Rome, Italy

[3] Univ Padua, Dept Biol, Padua, Italy

[4] IRCCS, European Inst Oncol IEO, Dept Expt Oncol, I-20139 Milan, Italy

[5] IRCCS Regina Elena Natl Canc Inst, Dept Res Adv Diagnost & Technol Innovat Translat R, SAFU Lab, Rome, Italy

[6] Fdn IRCCS Ist Neurol Carlo Besta, SC Neurol Neuroncol 2, Milan, Italy

[7] IRCCS Osped Policlin San Martino, Genoa, Italy

[8] Univ Genoa, Dipartimento Med Sperimentale, Genoa, Italy

[9] IRCCS San Raffaele Hosp, Div Neurosci, Neural Stem Cell Biol Unit, Via Olgettina 58, Milan, Italy

[10] Univ Piemonte Orientale, Dept Translat Med, Novara, Italy

[11] IRCCS Ist Romagnolo Studio Tumori IRST Dino Amador, Biosci Lab, Meldola, Italy

[12] Univ Cattolica S Cuore, Fdn Policlin Univ A Gemelli IRCCS, Dept Neurosurg, Largo A Gemelli 8, Rome, Italy

[13] Ist Super Sanita, Dept Oncol & Mol Med, Viale Regina Elena 299, I-00161 Rome, Italy

[14] Univ Padua, Dept Surg Oncol & Gastroenterol DiSCOG, Padua, Italy

来源：

JOURNAL OF NEURO-ONCOLOGY | 2023年 / 163卷 / 01期

关键词：

Glioblastoma; GBM stem-like cells (GSCs) lines; WES; RNA-seq; PROLIFERATION; KNOCKDOWN; MIGRATION; PROMOTES;

D O I：

10.1007/s11060-023-04287-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

PurposePatient-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).Methods94 (80 I surgery/14 II surgery) and 53 (42 I surgery/11 II surgery) GSCs lines underwent whole exome and trascriptome analysis, respectively.ResultsExome 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.ConclusionThe 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.

引用

页码：47 / 59

页数：13

共 22 条

[21] Genome-wide profiling of non-smoking-related lung cancer cells reveals common RB1 rearrangements associated with histopathologic transformation in EGFR-mutant tumors
Pros, E.
Saigi, M.
Alameda, D.
Gomez-Mariano, G.
Martinez-Delgado, B.
Alburquerque-Bejar, J. J.
Carretero, J.
Tonda, R.
Esteve-Codina, A.
Catala, I
Palmero, R.
Jove, M.
Lazaro, C.
Patino-Garcia, A.
Gil-Bazo, I
Verdura, S.
Teule, A.
Torres-Lanzas, J.
Sidransky, D.
Reguart, N.
Pio, R.
Juan-Vidal, O.
Nadal, E.
Felip, E.
Montuenga, L. M.
Sanchez-Cespedes, M.
ANNALS OF ONCOLOGY, 2020, 31 (02) : 274 - 282
[22] Genome-wide analysis of murine bone marrow-derived very small embryonic-like stem cells reveals that mitogenic growth factor signaling pathways play a crucial role in the quiescence and ageing of these cells
Mierzejewska, Katarzyna
Heo, Jinbeom
Kang, Jeong Wook
Kang, Hyunsook
Ratajczak, Janina
Ratajczak, Mariusz Z.
Kucia, Magda
Shin, Dong-Myung
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2013, 32 (02) : 281 - 290

← 1 2 3 →