title: LRP1B deletion is associated with poor outcome for glioblastoma patients.
abstract: BACKGROUND
  Deletion of the tumor suppressor gene LRP1B has been reported in glioblastoma, the most aggressive primary brain tumor in adults. Our objective was to analyze frequency and prognostic impact of LRP1B deletion and expression levels.
  
  
  METHODS
  We retrospectively included all the primary IDH1/2 wild-type GBM patients with available clinical follow-up, DNA and RNA from our database. Deletions were analyzed by SNP-array. LRP1B mRNA expression was analyzed by reverse transcription quantitative polymerase chain reaction.
  
  
  RESULTS
  178 patients were included with a median age of 62.36 years. LRP1B deletions were observed for 10.1% of patients (complete: 2.8%, partial: 7.3%). LRP1B deletions were associated with poor progression-free survival (PFS) (p=0.004) and overall survival (OS) (p=0.001). By multivariate analysis, LRP1B deletions remained significant for both PFS (p=0.003, hazard ratio (HR): 2.261) and OS (p=0.001, HR: 2.609). LRP1B was down expressed with a mean relative expression of 46% comparatively to normal tissue. No association between LRP1B mRNA and patient outcome was observed. No correlation was found between the deletions and the mRNA down-expression. These results were validated using GBM TCGA data.
  
  
  CONCLUSIONS
  LRP1B presents with frequent molecular alterations which impact patient outcome, highlighting the potential interest of this gene for glioblastoma patients.
authors.affiliation: Sorbonne Universités, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, INSERM U1127, CNRS UMR 7225, UPMC Paris 06, Paris 75013, France; AP-HP, Service de Neurologie 2, Groupe Hospitalier Pitié-Salpêtrière, Paris 75013, France.
authors.forename: E
authors.initials: E
authors.lastname: Tabouret
authors.affiliation: Sorbonne Universités, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, INSERM U1127, CNRS UMR 7225, UPMC Paris 06, Paris 75013, France.
authors.forename: M
authors.initials: M
authors.lastname: Labussière
authors.affiliation: Sorbonne Universités, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, INSERM U1127, CNRS UMR 7225, UPMC Paris 06, Paris 75013, France; AP-HP, Service de Neurologie 2, Groupe Hospitalier Pitié-Salpêtrière, Paris 75013, France.
authors.forename: A
authors.initials: A
authors.lastname: Alentorn
authors.affiliation: Sorbonne Universités, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, INSERM U1127, CNRS UMR 7225, UPMC Paris 06, Paris 75013, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Schmitt
authors.affiliation: Institut du Cerveau et de la Moelle épinière (ICM), Plateforme de Génotypage Séquençage, Paris 75013, France; OncoNeuroTek, Paris 75013, France.
authors.forename: Y
authors.initials: Y
authors.lastname: Marie
authors.affiliation: Sorbonne Universités, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, INSERM U1127, CNRS UMR 7225, UPMC Paris 06, Paris 75013, France; AP-HP, Service de Neurologie 2, Groupe Hospitalier Pitié-Salpêtrière, Paris 75013, France; OncoNeuroTek, Paris 75013, France. Electronic address: marc.sanson@psl.aphp.fr.
authors.forename: M
authors.initials: M
authors.lastname: Sanson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D018572:Disease-Free Survival; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D020641:Polymorphism, Single Nucleotide; D011973:Receptors, LDL / Q000235:genetics*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: C434476:LRP1B protein, human; D011973:Receptors, LDL
keywords: Deletion; Expression; Glioblastoma; LRP1B; Prognostic; SNP-array