title: Age-dependent prognostic effects of genetic alterations in glioblastoma.
abstract: OBJECTIVE
  Although the genetic alterations in glioblastoma have been well characterized, reports regarding their prognostic effects have been inconsistent.
  
  
  METHODS
  In this series of 140 consecutive cases of glioblastoma treated at a single center, we analyzed the frequency, age dependency and prognostic effects of TP53 mutation, CDKN2A/p16 deletion, EGFR amplification, as well as loss of chromosome 1p, chromosome 10q, and chromosome 19q. The complete set of genetic alterations was available on 60 of 140 patients.
  
  
  RESULTS
  In this cohort of glioblastoma cases, TP53 mutation was significantly associated with patient age. The prognostic effects of TP53 mutation, EGFR amplification, CDKN2A/p16 alterations, and loss of chromosome 1p were dependent on the age of the patient.
  
  
  CONCLUSIONS
  This is the first observation that the prognostic effects of TP53, 1p, and CDKN2A/p16 alterations are dependent on patient age. These observations concerning the interactions of age and genetic changes in glioblastoma suggest that tumorigenic pathways to glioblastoma vary with the age of the patient and that future molecular marker studies should carefully evaluate the potential age-dependent prognostic effects of these biological variables. The inconsistent or negative prognostic effects of molecular markers reported in prior studies of glioblastoma may be because different effects at different ages may have resulted in a cancellation of an overall effect in the entire cohort.
authors.affiliation: Molecular Neuro-Oncology Laboratory, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. tbatchelor@partners.org
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Batchelor
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Betensky
authors.forename: J Matthew
authors.initials: JM
authors.lastname: Esposito
authors.forename: Loc-Duyen D
authors.initials: LD
authors.lastname: Pham
authors.forename: Molly V
authors.initials: MV
authors.lastname: Dorfman
authors.forename: Nicole
authors.initials: N
authors.lastname: Piscatelli
authors.forename: Sarah
authors.initials: S
authors.lastname: Jhung
authors.forename: David
authors.initials: D
authors.lastname: Rhee
authors.forename: David N
authors.initials: DN
authors.lastname: Louis
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D005787:Gene Frequency; D005909:Glioblastoma / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53; D066246:ErbB Receptors