title: Multi-omics analysis of primary glioblastoma cell lines shows recapitulation of pivotal molecular features of parental tumors.
abstract: Glioblastoma (GBM) is the deadliest primary brain cancer in adults. Emerging innovative therapies hold promise for personalized cancer treatment. Improving therapeutic options depends on research relying on relevant preclinical models. In this line we have established in the setting of the GlioTex project (GBM and Experimental Therapeutics) a GBM patient-derived cell line (GBM-PDCL) library. A multi-omic approach was used to determine the molecular landscape of PDCL and the extent to which they represent GBM tumors.
  
  
  
  Single nucleotide polymorphism array, expression arrays, exome sequencing, and RNA sequencing were used to measure and compare the molecular landscapes of 20 samples representing 10 human GBM tumors and paired GBM-PDCLs.
  
  
  
  Copy number variations were similar for a median of 85% of the genome and for 59% of the major focal events. Somatic point mutations were similar in a median of 41%. Mutations in GBM driver and "druggable" genes were maintained in 67% of events. Mutations that were not conserved in the PDCL were mainly low allelic fraction and/or non-driver mutations. Based on RNA expression profiling, PDCLs cluster closely to their parental tumor with overexpression of pathways associated with cancer progression in PDCL.
  
  
  
  Overall, PDCLs recapitulate pivotal molecular alterations of paired-parental tumors supporting their use as a preclinical model of GBM. However, some driver aberrations are lost or gained in the passage from tumor to PDCL. Our results support using PDCL as a relevant preclinical model of GBM. Further investigations of changes between PDCLs and their parental tumor may provide insights into GBM biology.
authors: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.|Hadassah - Hebrew University Medical Center, Israel.
authors: Shai
authors: S
authors: Rosenberg
authors: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
authors: Maïté
authors: M
authors: Verreault
authors: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
authors: Charlotte
authors: C
authors: Schmitt
authors: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
authors: Justine
authors: J
authors: Guegan
authors: Bioinformatics/Biostatistics Core Facility, IHU-A-ICM, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
authors: Jeremy
authors: J
authors: Guehennec
authors: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
authors: Camille
authors: C
authors: Levasseur
authors: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.|Institut du Cerveau et de la Moelle épinière (ICM), Plateforme de Génotypage Séquençage, Paris, France.
authors: Yannick
authors: Y
authors: Marie
authors: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.|AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neuropathologie-Escourolle, Paris, France.
authors: Franck
authors: F
authors: Bielle
authors: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.|AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neuropathologie-Escourolle, Paris, France.
authors: Karima
authors: K
authors: Mokhtari
authors: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.|AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Paris, France.
authors: Khê
authors: K
authors: Hoang-Xuan
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors: Keith
authors: K
authors: Ligon
authors: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.|AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Paris, France.
authors: Marc
authors: M
authors: Sanson
authors: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.|AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Paris, France.
authors: Jean-Yves
authors: JY
authors: Delattre
authors: Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.|AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Paris, France.
authors: Ahmed
authors: A
authors: Idbaih
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations / Q000235:genetics*; D059472:Exome / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger
keywords: cancer; cell lines; genome; glioblastoma