title: Phenotype restricted genome-wide association study using a gene-centric approach identifies three low-risk neuroblastoma susceptibility Loci.
abstract: Neuroblastoma is a malignant neoplasm of the developing sympathetic nervous system that is notable for its phenotypic diversity. High-risk patients typically have widely disseminated disease at diagnosis and a poor survival probability, but low-risk patients frequently have localized tumors that are almost always cured with little or no chemotherapy. Our genome-wide association study (GWAS) has identified common variants within FLJ22536, BARD1, and LMO1 as significantly associated with neuroblastoma and more robustly associated with high-risk disease. Here we show that a GWAS focused on low-risk cases identified SNPs within DUSP12 at 1q23.3 (P = 2.07 × 10⁻⁶), DDX4 and IL31RA both at 5q11.2 (P = 2.94 × 10⁻⁶ and 6.54 × 10⁻⁷ respectively), and HSD17B12 at 11p11.2 (P = 4.20 × 10⁻⁷) as being associated with the less aggressive form of the disease. These data demonstrate the importance of robust phenotypic data in GWAS analyses and identify additional susceptibility variants for neuroblastoma.
authors: Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
authors: Le B
authors: le B
authors: Nguyen
authors: Sharon J
authors: SJ
authors: Diskin
authors: Mario
authors: M
authors: Capasso
authors: Kai
authors: K
authors: Wang
authors: Maura A
authors: MA
authors: Diamond
authors: Joseph
authors: J
authors: Glessner
authors: Cecilia
authors: C
authors: Kim
authors: Edward F
authors: EF
authors: Attiyeh
authors: Yael P
authors: YP
authors: Mosse
authors: Kristina
authors: K
authors: Cole
authors: Achille
authors: A
authors: Iolascon
authors: Marcella
authors: M
authors: Devoto
authors: Hakon
authors: H
authors: Hakonarson
authors: Hongzhe K
authors: HK
authors: Li
authors: John M
authors: JM
authors: Maris
mesh_terms: D000465:Algorithms; D002675:Child, Preschool; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D007223:Infant; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide