Phenotype Restricted Genome-Wide Association Study Using a Gene-Centric Approach Identifies Three Low-Risk Neuroblastoma Susceptibility Loci

被引：95

作者：

Nguyen, Le B. ^{[1
,2
,3
]}

Diskin, Sharon J. ^{[1
,2
]}

Capasso, Mario ^{[4
,5
]}

Wang, Kai ^{[6
]}

Diamond, Maura A. ^{[1
,2
]}

Glessner, Joseph ^{[6
]}

Kim, Cecilia ^{[6
]}

Attiyeh, Edward F. ^{[1
,2
,7
]}

Mosse, Yael P. ^{[1
,2
,7
]}

Cole, Kristina ^{[1
,2
,7
]}

Iolascon, Achille ^{[4
,5
]}

Devoto, Marcella ^{[8
]}

Hakonarson, Hakon ^{[6
,7
,8
]}

Li, Hongzhe K. ^{[3
]}

Maris, John M. ^{[1
,2
,5
,9
]}

机构：

[1] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA

[2] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA

[3] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA

[4] Univ Naples Federico 2, Dept Biochem & Med Biotechnol, Naples, Italy

[5] CEINGE Biotecnol Avanzate, Naples, Italy

[6] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA

[7] Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA

[8] Childrens Hosp Philadelphia, Div Genet, Philadelphia, PA 19104 USA

[9] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA

来源：

PLOS GENETICS | 2011年 / 7卷 / 03期

关键词：

N-MYC; SET; AMPLIFICATION;

D O I：

10.1371/journal.pgen.1002026

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 x 10(-6)), DDX4 and IL31RA both at 5q11.2 (P = 2.94 x 10(-6) and 6.54 x 10(-7) respectively), and HSD17B12 at 11p11.2 (P = 4.20 x 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.

引用

页数：9

共 18 条

[1] International consensus for neuroblastoma molecular diagnostics: report from the International Neuroblastoma Risk Group (INRG) Biology Committee [J].

Ambros, P. F. ;

Ambros, I. M. ;

Brodeur, G. M. ;

Haber, M. ;

Khan, J. ;

Nakagawara, A. ;

Schleiermacher, G. ;

Speleman, F. ;

Spitz, R. ;

London, W. B. ;

Cohn, S. L. ;

Pearson, A. D. J. ;

Maris, J. M. .

BRITISH JOURNAL OF CANCER, 2009, 100 (09) :1471-1482

[2]

BRESLOW N, 1971, CANCER RES, V31, P2098

[3] AMPLIFICATION OF N-MYC IN UNTREATED HUMAN NEUROBLASTOMAS CORRELATES WITH ADVANCED DISEASE STAGE [J].

BRODEUR, GM ;

SEEGER, RC ;

SCHWAB, M ;

VARMUS, HE ;

BISHOP, JM .

SCIENCE, 1984, 224 (4653) :1121-1124

[4] REVISIONS OF THE INTERNATIONAL CRITERIA FOR NEUROBLASTOMA DIAGNOSIS, STAGING, AND RESPONSE TO TREATMENT [J].

BRODEUR, GM ;

PRITCHARD, J ;

BERTHOLD, F ;

CARLSEN, NLT ;

CASTEL, V ;

CASTLEBERRY, RP ;

DEBERNARDI, B ;

EVANS, AE ;

FAVROT, M ;

HEDBORG, F ;

KANEKO, M ;

KEMSHEAD, J ;

LAMPERT, F ;

LEE, REJ ;

LOOK, AT ;

PEARSON, ADJ ;

PHILIP, T ;

ROALD, B ;

SAWADA, T ;

SEEGER, RC ;

TSUCHIDA, Y ;

VOUTE, PA .

JOURNAL OF CLINICAL ONCOLOGY, 1993, 11 (08) :1466-1477

[5] Common variations in BARD1 influence susceptibility to high-risk neuroblastoma [J].

Capasso, Mario ;

Devoto, Marcella ;

Hou, Cuiping ;

Asgharzadeh, Shahab ;

Glessner, Joseph T. ;

Attiyeh, Edward F. ;

Mosse, Yael P. ;

Kim, Cecilia ;

Diskin, Sharon J. ;

Cole, Kristina A. ;

Bosse, Kristopher ;

Diamond, Maura ;

Laudenslager, Marci ;

Winter, Cynthia ;

Bradfield, Jonathan P. ;

Scott, Richard H. ;

Jagannathan, Jayanti ;

Garris, Maria ;

McConville, Carmel ;

London, Wendy B. ;

Seeger, Robert C. ;

Grant, Struan F. A. ;

Li, Hongzhe ;

Rahman, Nazneen ;

Rappaport, Eric ;

Hakonarson, Hakon ;

Maris, John M. .

NATURE GENETICS, 2009, 41 (06) :718-723

[6] Copy number variation at 1q21.1 associated with neuroblastoma [J].

Diskin, Sharon J. ;

Hou, Cuiping ;

Glessner, Joseph T. ;

Attiyeh, Edward F. ;

Laudenslager, Marci ;

Bosse, Kristopher ;

Cole, Kristina ;

Mosse, Yael P. ;

Wood, Andrew ;

Lynch, Jill E. ;

Pecor, Katlyn ;

Diamond, Maura ;

Winter, Cynthia ;

Wang, Kai ;

Kim, Cecilia ;

Geiger, Elizabeth A. ;

McGrady, Patrick W. ;

Blakemore, Alexandra I. F. ;

London, Wendy B. ;

Shaikh, Tamim H. ;

Bradfield, Jonathan ;

Grant, Struan F. A. ;

Li, Hongzhe ;

Devoto, Marcella ;

Rappaport, Eric R. ;

Hakonarson, Hakon ;

Maris, John M. .

NATURE, 2009, 459 (7249) :987-U112

[7] A global test for groups of genes: testing association with a clinical outcome [J].

Goeman, JJ ;

van de Geer, SA ;

de Kort, F ;

van Houwelingen, HC .

BIOINFORMATICS, 2004, 20 (01) :93-99

[8]

Harris MA, 2008, NUCLEIC ACIDS RES, V36, pD440, DOI 10.1093/nar/gkm883

[9] The UCSC Genome Browser Database: update 2006 [J].

Hinrichs, A. S. ;

Karolchik, D. ;

Baertsch, R. ;

Barber, G. P. ;

Bejerano, G. ;

Clawson, H. ;

Diekhans, M. ;

Furey, T. S. ;

Harte, R. A. ;

Hsu, F. ;

Hillman-Jackson, J. ;

Kuhn, R. M. ;

Pedersen, J. S. ;

Pohl, A. ;

Raney, B. J. ;

Rosenbloom, K. R. ;

Siepel, A. ;

Smith, K. E. ;

Sugnet, C. W. ;

Sultan-Qurraie, A. ;

Thomas, D. J. ;

Trumbower, H. ;

Weber, R. J. ;

Weirauch, M. ;

Zweig, A. S. ;

Haussler, D. ;

Kent, W. J. .

NUCLEIC ACIDS RESEARCH, 2006, 34 :D590-D598

[10] CLINICAL RELEVANCE OF TUMOR-CELL PLOIDY AND N-MYC GENE AMPLIFICATION IN CHILDHOOD NEUROBLASTOMA - A PEDIATRIC ONCOLOGY GROUP-STUDY [J].

LOOK, AT ;

HAYES, FA ;

SHUSTER, JJ ;

DOUGLAS, EC ;

CASTLEBERRY, RP ;

BOWMAN, LC ;

SMITH, EI ;

BRODEUR, GM .

JOURNAL OF CLINICAL ONCOLOGY, 1991, 9 (04) :581-591

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