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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.
SUBMITTER: Holdhoff M
PROVIDER: S-EPMC5482595 | biostudies-literature | 2017 May
REPOSITORIES: biostudies-literature
Holdhoff Matthias M Cairncross Gregory J GJ Kollmeyer Thomas M TM Zhang Ming M Zhang Peixin P Mehta Minesh P MP Werner-Wasik Maria M Souhami Luis L Bahary Jean-Paul JP Kwok Young Y Hartford Alan C AC Chakravarti Arnab A Yegnasubramanian Srinivasan S Vogelstein Bert B Papadopoulos Nickolas N Kinzler Kenneth K Jenkins Robert B RB Bettegowda Chetan C
Oncotarget 20170501 22
<h4>Background</h4>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.<h4>Methods</h4> ...[more]