Chromosome 6p22 Locus Associated with Clinically Aggressive Neuroblastoma.

@article{citeulike:2792468, abstract = {BACKGROUND: Neuroblastoma is a malignant condition of the developing sympathetic nervous system that most commonly affects young children and is often lethal. Its cause is not known. METHODS: We performed a genomewide association study by first genotyping blood DNA samples from 1032 patients with neuroblastoma and 2043 control subjects of European descent using the Illumina HumanHap550 BeadChip. Samples from three independent groups of patients with neuroblastoma (a total of 720 patients) and 2128 control subjects were then genotyped to replicate significant associations. RESULTS: We observed a significant association between neuroblastoma and the common minor alleles of three consecutive single-nucleotide polymorphisms (SNPs) at chromosome band 6p22 and containing the predicted genes FLJ22536 and FLJ44180 (P=1.71x10(-9) to 7.01x10(-10); allelic odds ratio, 1.39 to 1.40). Homozygosity for the at-risk G allele of the most significantly associated SNP, rs6939340, resulted in an increased likelihood of the development of neuroblastoma (odds ratio, 1.97; 95\% confidence interval, 1.58 to 2.45). Subsequent genotyping of the three 6p22 SNPs in three independent case series confirmed our observation of an association (P=9.33x10(-15) at rs6939340 for joint analysis). Patients with neuroblastoma who were homozygous for the risk alleles at 6p22 were more likely to have metastatic (stage 4) disease (P=0.02), amplification of the MYCN oncogene in the tumor cells (P=0.006), and disease relapse (P=0.01). CONCLUSIONS: A common genetic variation at chromosome band 6p22 is associated with susceptibility to neuroblastoma. Copyright 2008 Massachusetts Medical Society.}, address = {From the Division of Oncology and the Center for Childhood Cancer Research (J.M.M., Y.P.M., C.H., E.F.A., S.J.D., M.L., C.W., K.A.C., E.F.R.), the Center for Applied Genomics ( J.P.B., J.T.G., C.K., E.C.F., T.C., A.W.E., S.F.A.G., H.H.), and the Division of Genetics (M.C., M.D., S.F.A.G., H.H.), Children's Hospital of Philadelphia; and the Department of Pediatrics (J.M.M., Y.P.M., C.H., E.F.A., S.J.D., M.L., C.W., K.A.C., E.F.R.), the Abramson Family Cancer Research Institute, (J.M.M.), the Department of Biostatistics and Epidemiology (S.M., M.D., H.L.), and the Department of Pediatrics (M.C., M.D., S.F.A.G., H.H.), University of Pennsylvania School of Medicine — all in Philadelphia; the Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom (R.H.S., N.R.); the Division of Hematology–Oncology and the Saban Research Institute, Children's Hospital Los Angeles, and the Keck School of Medicine, University of Southern California — both in Los Angeles (S.A., R.C.S.); Federico II University, Centro di Ingegneria Genetica Biotecnologie Avanzate, Naples, Italy (M.C.); the Division of Reproductive and Child Health and CRUK Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom (C.M.); the Department of Statistics, University of Florida, and the Children's Oncology Group — both in Gainesville (W.B.L.); and the Department of Experimental Medicine, La Sapienza University of Rome, Rome (M.D.). Dr. Mosse and Mr. Bradfield contributed equally to this article.This article (10.1056/NEJMoa0708698) was published at www.nejm.org on May 7, 2008. It will appear in the June 12 issue of the Journal.}, author = {Maris, John M M. and Mosse, Yael P P. and Bradfield, Jonathan P P. and Hou, Cuiping and Monni, Stefano and Scott, Richard H H. and Asgharzadeh, Shahab and Attiyeh, Edward F F. and Diskin, Sharon J J. and Laudenslager, Marci and Winter, Cynthia and Cole, Kristina A A. and Glessner, Joseph T T. and Kim, Cecilia and Frackelton, Edward C C. and Casalunovo, Tracy and Eckert, Andrew W W. and Capasso, Mario and Rappaport, Eric F F. and McConville, Carmel and London, Wendy B B. and Seeger, Robert C C. and Rahman, Nazneen and Devoto, Marcella and Grant, Struan F A F. and Li, Hongzhe and Hakonarson, Hakon }, citeulike-article-id = {2792468}, doi = {http://dx.doi.org/10.1056/NEJMoa0708698}, issn = {1533-4406}, journal = {The New England journal of medicine}, keywords = {neuroblastoma}, month = {May}, posted-at = {2008-05-13 04:17:24}, priority = {2}, title = {Chromosome 6p22 Locus Associated with Clinically Aggressive Neuroblastoma.}, url = {http://dx.doi.org/10.1056/NEJMoa0708698}, year = {2008} }

TY - JOUR ID - citeulike:2792468 L3 - citeulike-article-id:2792468 TI - Chromosome 6p22 Locus Associated with Clinically Aggressive Neuroblastoma. JF - The New England journal of medicine AD - From the Division of Oncology and the Center for Childhood Cancer Research (J.M.M., Y.P.M., C.H., E.F.A., S.J.D., M.L., C.W., K.A.C., E.F.R.), the Center for Applied Genomics ( J.P.B., J.T.G., C.K., E.C.F., T.C., A.W.E., S.F.A.G., H.H.), and the Division of Genetics (M.C., M.D., S.F.A.G., H.H.), Children's Hospital of Philadelphia; and the Department of Pediatrics (J.M.M., Y.P.M., C.H., E.F.A., S.J.D., M.L., C.W., K.A.C., E.F.R.), the Abramson Family Cancer Research Institute, (J.M.M.), the Department of Biostatistics and Epidemiology (S.M., M.D., H.L.), and the Department of Pediatrics (M.C., M.D., S.F.A.G., H.H.), University of Pennsylvania School of Medicine — all in Philadelphia; the Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey, United Kingdom (R.H.S., N.R.); the Division of Hematology–Oncology and the Saban Research Institute, Children's Hospital Los Angeles, and the Keck School of Medicine, University of Southern California — both in Los Angeles (S.A., R.C.S.); Federico II University, Centro di Ingegneria Genetica Biotecnologie Avanzate, Naples, Italy (M.C.); the Division of Reproductive and Child Health and CRUK Institute for Cancer Studies, University of Birmingham, Birmingham, United Kingdom (C.M.); the Department of Statistics, University of Florida, and the Children's Oncology Group — both in Gainesville (W.B.L.); and the Department of Experimental Medicine, La Sapienza University of Rome, Rome (M.D.). Dr. Mosse and Mr. Bradfield contributed equally to this article.This article (10.1056/NEJMoa0708698) was published at www.nejm.org on May 7, 2008. It will appear in the June 12 issue of the Journal. SN - 1533-4406 N2 - BACKGROUND: Neuroblastoma is a malignant condition of the developing sympathetic nervous system that most commonly affects young children and is often lethal. Its cause is not known. METHODS: We performed a genomewide association study by first genotyping blood DNA samples from 1032 patients with neuroblastoma and 2043 control subjects of European descent using the Illumina HumanHap550 BeadChip. Samples from three independent groups of patients with neuroblastoma (a total of 720 patients) and 2128 control subjects were then genotyped to replicate significant associations. RESULTS: We observed a significant association between neuroblastoma and the common minor alleles of three consecutive single-nucleotide polymorphisms (SNPs) at chromosome band 6p22 and containing the predicted genes FLJ22536 and FLJ44180 (P=1.71x10(-9) to 7.01x10(-10); allelic odds ratio, 1.39 to 1.40). Homozygosity for the at-risk G allele of the most significantly associated SNP, rs6939340, resulted in an increased likelihood of the development of neuroblastoma (odds ratio, 1.97; 95% confidence interval, 1.58 to 2.45). Subsequent genotyping of the three 6p22 SNPs in three independent case series confirmed our observation of an association (P=9.33x10(-15) at rs6939340 for joint analysis). Patients with neuroblastoma who were homozygous for the risk alleles at 6p22 were more likely to have metastatic (stage 4) disease (P=0.02), amplification of the MYCN oncogene in the tumor cells (P=0.006), and disease relapse (P=0.01). CONCLUSIONS: A common genetic variation at chromosome band 6p22 is associated with susceptibility to neuroblastoma. Copyright 2008 Massachusetts Medical Society. KW - neuroblastoma AU - Maris, John M AU - Mosse, Yael P AU - Bradfield, Jonathan P AU - Hou, Cuiping AU - Monni, Stefano AU - Scott, Richard H AU - Asgharzadeh, Shahab AU - Attiyeh, Edward F AU - Diskin, Sharon J AU - Laudenslager, Marci AU - Winter, Cynthia AU - Cole, Kristina A AU - Glessner, Joseph T AU - Kim, Cecilia AU - Frackelton, Edward C AU - Casalunovo, Tracy AU - Eckert, Andrew W AU - Capasso, Mario AU - Rappaport, Eric F AU - McConville, Carmel AU - London, Wendy B AU - Seeger, Robert C AU - Rahman, Nazneen AU - Devoto, Marcella AU - Grant, Struan F A AU - Li, Hongzhe AU - Hakonarson, Hakon PY - 2008/05/07/ UR - http://dx.doi.org/10.1056/NEJMoa0708698 ER -