Your browser doesn't support javascript.
loading
Integrating cell-based and clinical genome-wide studies to identify genetic variants contributing to treatment failure in neuroblastoma patients.
Pinto, N; Gamazon, E R; Antao, N; Myers, J; Stark, A L; Konkashbaev, A; Im, H K; Diskin, S J; London, W B; Ludeman, S M; Maris, J M; Cox, N J; Cohn, S L; Dolan, M E.
Affiliation
  • Pinto N; Section of Pediatric Hematology/Oncology, Department of Pediatrics, The University of Chicago, Chicago, Illinois, USA.
  • Gamazon ER; Section of Genetic Medicine, Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
  • Antao N; Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
  • Myers J; Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
  • Stark AL; Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
  • Konkashbaev A; Section of Genetic Medicine, Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
  • Im HK; Department of Health Studies, The University of Chicago, Chicago, Illinois, USA.
  • Diskin SJ; Division of Oncology and Center for Childhood Cancer Research, The Children's Hospital of Philadelphia and Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • London WB; 1] Boston Children's Hospital/Dana Farber Harvard Cancer Center, Harvard University, Boston, Massachusetts, USA [2] Children's Oncology Group Statistics and Data Center, Arcadia, California, USA.
  • Ludeman SM; Department of Basic and Social Sciences, Albany College of Pharmacy and Health Sciences, Albany, New York, USA.
  • Maris JM; Division of Oncology and Center for Childhood Cancer Research, The Children's Hospital of Philadelphia and Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Cox NJ; Section of Genetic Medicine, Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
  • Cohn SL; Section of Pediatric Hematology/Oncology, Department of Pediatrics, The University of Chicago, Chicago, Illinois, USA.
  • Dolan ME; Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois, USA.
Clin Pharmacol Ther ; 95(6): 644-52, 2014 Jun.
Article in En | MEDLINE | ID: mdl-24549002
ABSTRACT
High-risk neuroblastoma is an aggressive malignancy, with high rates of treatment failure. We evaluated genetic variants associated with in vitro sensitivity to two derivatives of cyclophosphamide for association with clinical response in a separate replication cohort of neuroblastoma patients (n = 2,709). To determine sensitivity, lymphoblastoid cell lines (LCLs) were exposed to increasing concentrations of 4-hydroperoxycyclophosphamide (4HC; n = 422) and phosphoramide mustard (PM; n = 428). Genome-wide association studies were performed to identify single-nucleotide polymorphisms (SNPs) associated with sensitivity to 4HC and PM. SNPs consistently associated with LCL sensitivity were analyzed for associations with event-free survival (EFS) in patients. Two linked SNPs, rs9908694 and rs1453560, were found to be associated with (i) sensitivity to PM in LCLs across populations and (ii) EFS in all patients (P = 0.01) and within the high-risk subset (P = 0.05). Our study highlights the value of cell-based models to identify candidate variants that may predict response to treatment in patients with cancer.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain Neoplasms / Genome-Wide Association Study / Neuroblastoma Type of study: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Child / Humans Language: En Journal: Clin Pharmacol Ther Year: 2014 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain Neoplasms / Genome-Wide Association Study / Neuroblastoma Type of study: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Child / Humans Language: En Journal: Clin Pharmacol Ther Year: 2014 Document type: Article