Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Machiela MJ, Grunewald TGP, Surdez D, Reynaud S, Mirabeau O, Karlins E, Rubio RA, Zaidi S, Grossetete-Lalami S, Ballet S, Lapouble E, Laurence V, Michon J, Pierron G, Kovar H, Gaspar N, Kontny U, Gonzalez-Neira A, Picci P, Alonso J, Patino-Garcia A, Corradini N, Berard PM, Freedman ND, Rothman N, Dagnall CL, Burdett L, Jones K, Manning M, Wyatt K, Zhou W, Yeager M, Cox DG, Hoover RN, Khan J, Armstrong GT, Leisenring WM, Bhatia S, Robison LL, Kulozik AE, Kriebel J, Meitinger T, Metzler M, Hartmann W, Strauch K, Kirchner T, Dirksen U, Morton LM, Mirabello L, Tucker MA, Tirode F, Chanock SJ, Delattre O
Zeitschrift: Nature Communications
Jahr der Veröffentlichung: 2018
Band: 9
Heftnummer: 1
ISSN: 2041-1723


Abstract

Ewing sarcoma (EWS) is a pediatric cancer characterized by the EWSR1-FLI1 fusion. We performed a genome-wide association study of 733 EWS cases and 1346 unaffected individuals of European ancestry. Our study replicates previously reported susceptibility loci at 1p36.22, 10q21.3 and 15q15.1, and identifies new loci at 6p25.1, 20p11.22 and 20p11.23. Effect estimates exhibit odds ratios in excess of 1.7, which is high for cancer GWAS, and striking in light of the rarity of EWS cases in familial cancer syndromes. Expression quantitative trait locus (eQTL) analyses identify candidate genes at 6p25.1 (RREB1) and 20p11.23 (KIZ). The 20p11.22 locus is near NKX2-2, a highly overexpressed gene in EWS. Interestingly, most loci reside near GGAA repeat sequences and may disrupt binding of the EWSR1-FLI1 fusion protein. The high locus to case discovery ratio from 733 EWS cases suggests a genetic architecture in which moderate risk SNPs constitute a significant fraction of risk.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Metzler, Markus PD Dr.
Professur für Kinder- und Jugendmedizin mit dem Schwerpunkt Pädiatrische Onkologie und Hämatologie


Einrichtungen weiterer Autorinnen und Autoren

Centre Léon-Bérard (UNICANCER)
Deutsches Krebsforschungszentrum (DKFZ)
Fred Hutchinson Cancer Research Center
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU)
Institut Curie
Institut Gustave-Roussy
Istituto Ortopedico Rizzoli (IRCCS)
Ludwig-Maximilians-Universität (LMU)
National Cancer Institute (NCI)
PSL Research University / Université de recherche Paris Sciences et Lettres
Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen
Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO)
St. Anna Kinderkrebsforschung
St. Jude Children’s Research Hospital
Universidad Carlos III de Madrid (UC3M)
Universidad de Navarra
Universitätsklinikum Essen
Universitätsklinikum Heidelberg
Universitätsklinikum Münster
Université Claude Bernard Lyon 1 (UCB)
University of Alabama at Birmingham (UAB)


Zitierweisen

APA:
Machiela, M.J., Grunewald, T.G.P., Surdez, D., Reynaud, S., Mirabeau, O., Karlins, E.,... Delattre, O. (2018). Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility. Nature Communications, 9(1). https://dx.doi.org/10.1038/s41467-018-05537-2

MLA:
Machiela, Mitchell J., et al. "Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility." Nature Communications 9.1 (2018).

BibTeX: 

Zuletzt aktualisiert 2019-22-03 um 22:08