Phenotype Restricted Genome-Wide Association Study Using a Gene-Centric Approach Identifies Three Low-Risk Neuroblastoma Susceptibility Loci
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.
Vyšlo v časopise:
Phenotype Restricted Genome-Wide Association Study Using a Gene-Centric Approach Identifies Three Low-Risk Neuroblastoma Susceptibility Loci. PLoS Genet 7(3): e32767. doi:10.1371/journal.pgen.1002026
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1002026
Souhrn
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.
Zdroje
1. MarisJM 2010 Recent advances in neuroblastoma. N Engl J Med 362 2202 2211
2. BrodeurGMPritchardJBertholdFCarlsenNLCastelV 1993 Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment. J Clin Oncol 11 1466 1477
3. AmbrosPFAmbrosIMBrodeurGMHaberMKhanJ 2009 International consensus for neuroblastoma molecular diagnostics: report from the International Neuroblastoma Risk Group (INRG) Biology Committee. Br J Cancer 100 1471 1482
4. MarisJMMosseYPBradfieldJPHouCMonniS 2008 Chromosome 6p22 Locus Associated with Clinically Aggressive Neuroblastoma. N Engl J Med 358 2585 2593
5. CapassoMDevotoMHouCAsgharzadehSGlessnerJT 2009 Common variations in BARD1 influence susceptibility to high-risk neuroblastoma. Nat Genet 41 718 723
6. WangKDiskinSJZhangHAttiyehEFWinterC 2011 Integrative genomics identifies LMO1 as a neuroblastoma oncogene. Nature 469 216 220
7. DiskinSJHouCGlessnerJTAttiyehEFLaudenslagerM 2009 Copy number variation at 1q21.1 associated with neuroblastoma. Nature 459 987 991
8. GoemanJJvan de GeerSAde KortFvan HouwelingenHC 2004 A global test for groups of genes: testing association with a clinical outcome. Bioinformatics 20 93 99
9. HinrichsASKarolchikDBaertschRBarberGPBejeranoG 2006 The UCSC Genome Browser Database: update 2006. Nucleic Acids Res 34 D590 598
10. PurcellSNealeBTodd-BrownKThomasLFerreiraMA 2007 PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81 559 575
11. NewtonMAQuintanaFADen BoonJASenguptaSAhquistP 2007 Random-set methods identify distinct aspects of the enrichment signal in gene-set analysis. Ann Appl Stat 1 85 106
12. SubramanianAKuehnHGouldJTamayoPMesirovJP 2007 GSEA-P: a desktop application for Gene Set Enrichment Analysis. Bioinformatics 23 3251 3253
13. Gene Ontology Consortium 2008 The Gene Ontology project in 2008. Nucleic Acids Res 36 D440 4
14. BreslowNMcCannB 1971 Statistical estimation of prognosis for children with neuroblastoma. Cancer Res 31 2098 2103
15. ShimadaHAmbrosIMDehnerLPHataJJoshiVV 1999 The International Neuroblastoma Pathology Classification (the Shimada system). Cancer 86 364 372
16. LookATHayesFAShusterJJDouglassECCastleberryRP 1991 Clinical relevance of tumor cell ploidy and N-myc gene amplification in childhood neuroblastoma: a Pediatric Oncology Group study. J Clin Oncol 9 581 591
17. BrodeurGMSeegerRCSchwabMVarmusHEBishopJM 1984 Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science 224 1121 1124
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2011 Číslo 3
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