title: Genetic landscape of extreme responders with anaplastic oligodendroglioma.
abstract: BACKGROUND
  The NRG Oncology RTOG 9402 trial showed significant survival benefit in patients with 1p/19q co-deleted anaplastic oligodendrogliomas (AO) who received both radiation (RT) and chemotherapy (PCV regimen) versus RT alone. Substantial separation of the survival curves was only seen after 7.3 years. We aimed to determine whether there are specific genetic alterations that distinguish co-deleted AO patients who benefit from the addition of PCV from those who do not.
  
  
  METHODS
  We performed whole exome sequencing on matched tumor and normal DNA from all available short-term (STS) and long-term survivors (LTS) who received RT+PCV. hTERT status and rs55705857 genotypes (G-allele) were analyzed in both cohorts.
  
  
  RESULTS
  Six STS (survival of <7.3y) and 7 LTS (survival of ≥7.3y and no progression) had sufficient material for analysis. There was no significant difference between the groups regarding age, performance status and extent of resection. On average, STS had 7 and LTS 4 mutations. Most common mutations in STS vs. LTS were: IDH1 (67 vs. 86%), CIC (50 vs. 71%) and FUBP1 (17 vs. 71%). The hTERT promoter was mutated in 83% STS and 86% LTS. Genotyping of rs55705857 showed a higher prevalence of G allele carriers in LTS than STS (43 vs. 17%).
  
  
  CONCLUSIONS
  These findings confirm that IDH, CIC, FUBP1 mutations and rs55705857 genotype are common in AO. No distinct genetic signature was identified to differentiate STS and LTS.
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Holdhoff
authors.affiliation: Charbonneau Cancer Institute at the University of Calgary, Calgary, AB, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Cairncross
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Kollmeyer
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: NRG Oncology Statistics and Data Management Center, Philadelphia, PA, USA.
authors.forename: Peixin
authors.initials: P
authors.lastname: Zhang
authors.affiliation: University of Maryland Medical Center, Baltimore, MD, USA.
authors.forename: Minesh P
authors.initials: MP
authors.lastname: Mehta
authors.affiliation: Thomas Jefferson University Hospital, Philadelphia, PA, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Werner-Wasik
authors.affiliation: McGill University Health Centre, Montreal, QC, Canada.
authors.forename: Luis
authors.initials: L
authors.lastname: Souhami
authors.affiliation: Centre Hospitalier de l'Université de Montréal, Montreal University, Montreal, QC, Canada.
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Bahary
authors.affiliation: University of Maryland Medical Center, Baltimore, MD, USA.
authors.forename: Young
authors.initials: Y
authors.lastname: Kwok
authors.affiliation: Darthmouth-Hitchcock Medical Center, Lebanon, NH, USA.
authors.forename: Alan C
authors.initials: AC
authors.lastname: Hartford
authors.affiliation: The Ohio State University, Columbus, OH, USA.
authors.forename: Arnab
authors.initials: A
authors.lastname: Chakravarti
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Yegnasubramanian
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
authors.forename: Bert
authors.initials: B
authors.lastname: Vogelstein
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
authors.forename: Nickolas
authors.initials: N
authors.lastname: Papadopoulos
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kinzler
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.affiliation: The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
authors.forename: Chetan
authors.initials: C
authors.lastname: Bettegowda
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1; D002888:Chromosomes, Human, Pair 19; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009837:Oligodendroglioma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor
keywords: chemotherapy; co-deletion 1p/19q; genomics; oligodendroglioma; survival