title: GBM-associated mutations and altered protein expression are more common in young patients.
abstract: BACKGROUND
  Geriatric glioblastoma (GBM) patients have a poorer prognosis than younger patients, but IDH1/2 mutations (more common in younger patients) confer a favorable prognosis. We compared key GBM molecular alterations between an elderly (age ≥ 70) and younger (18 < = age < = 45) cohort to explore potential therapeutic opportunities.
  
  
  RESULTS
  Alterations more prevalent in the young GBM cohort compared to the older cohort (P < 0.05) were: overexpression of ALK, RRM1, TUBB3 and mutation of ATRX, BRAF, IDH1, and TP53. However, PTEN mutation was significantly more frequent in older patients. Among patients with wild-type IDH1/2 status, TOPO1 expression was higher in younger patients, whereas MGMT methylation was more frequent in older patients. Within the molecularly-defined IDH wild-type GBM cohort, younger patients had significantly more mutations in PDGFRA, PTPN11, SMARCA4, BRAF and TP53.
  
  
  METHODS
  GBMs from 178 elderly patients and 197 young patients were analyzed using DNA sequencing, immunohistochemistry, in situ hybridization, and MGMT-methylation assay to ascertain mutational and amplification/expressional status.
  
  
  CONCLUSIONS
  Significant molecular differences occurred in GBMs from elderly and young patients. Except for the older cohort's more frequent PTEN mutation and MGMT methylation, younger patients had a higher frequency of potential therapeutic targets.
authors: Departments of Neurosurgery, Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors: Sherise D
authors: SD
authors: Ferguson
authors: Caris Life Sciences, Phoenix, AZ 85040, USA.
authors: Joanne
authors: J
authors: Xiu
authors: Departments of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors: Shiao-Pei
authors: SP
authors: Weathers
authors: Departments of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors: Shouhao
authors: S
authors: Zhou
authors: Department of Translational Neuro-Oncology and Neurotherapeutics, Pacific Neuroscience Institute and John Wayne Cancer Institute at Providence Saint John's Health Center, Santa Monica, CA 90404, USA.
authors: Santosh
authors: S
authors: Kesari
authors: Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
authors: Stephanie E
authors: SE
authors: Weiss
authors: Department of Genome Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, USA.
authors: Roeland G
authors: RG
authors: Verhaak
authors: Penn State Hershey Cancer Institute, Hershey, PA 17033, USA.
authors: Raymond J
authors: RJ
authors: Hohl
authors: Department of Neurology, Wayne State University, School of Medicine, Karmanos Cancer Center, Detroit, MI 48201, USA.
authors: Geoffrey R
authors: GR
authors: Barger
authors: Caris Life Sciences, Phoenix, AZ 85040, USA.
authors: Sandeep K
authors: SK
authors: Reddy
authors: Departments of Neurosurgery, Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors: Amy B
authors: AB
authors: Heimberger
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D015331:Cohort Studies; D019175:DNA Methylation; D004252:DNA Mutational Analysis / Q000379:methods; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009154:Mutation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors
keywords: DNA sequencing; GBM; mutational analysis