Genetic landscape of extreme responders with anaplastic oligodendroglioma

// Matthias Holdhoff 1 , Gregory J. Cairncross 2 , Thomas M. Kollmeyer 3 , Ming Zhang 1 , Peixin Zhang 4 , Minesh P. Mehta 5 , Maria Werner-Wasik 6 , Luis Souhami 7 , Jean-Paul Bahary 8 , Young Kwok 5 , Alan C. Hartford 9 , Arnab Chakravarti 10 , Srinivasan Yegnasubramanian 1 , Bert Vogelstein 1 , Nickolas Papadopoulos 1 , Kenneth Kinzler 1 , Robert B. Jenkins 3 and Chetan Bettegowda 1 1 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA 2 Charbonneau Cancer Institute at the University of Calgary, Calgary, AB, USA 3 Mayo Clinic, Rochester, MN, USA 4 NRG Oncology Statistics and Data Management Center, Philadelphia, PA, USA 5 University of Maryland Medical Center, Baltimore, MD, USA 6 Thomas Jefferson University Hospital, Philadelphia, PA, USA 7 McGill University Health Centre, Montreal, QC, Canada 8 Centre Hospitalier de l’Universite de Montreal, Montreal University, Montreal, QC, Canada 9 Darthmouth-Hitchcock Medical Center, Lebanon, NH, USA 10 The Ohio State University, Columbus, OH, USA Correspondence to: Matthias Holdhoff, email: // Chetan Bettegowda, email: // Keywords : oligodendroglioma, chemotherapy, survival, genomics, co-deletion 1p/19q Received : October 01, 2016 Accepted : March 21, 2017 Published : March 31, 2017 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