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Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility
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 iden...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2018
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085378/ https://www.ncbi.nlm.nih.gov/pubmed/30093639 http://dx.doi.org/10.1038/s41467-018-05537-2 |
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| author | Machiela, Mitchell J. Grünewald, Thomas G. P. Surdez, Didier Reynaud, Stephanie Mirabeau, Olivier Karlins, Eric Rubio, Rebeca Alba Zaidi, Sakina Grossetete-Lalami, Sandrine Ballet, Stelly Lapouble, Eve Laurence, Valérie Michon, Jean Pierron, Gaelle Kovar, Heinrich Gaspar, Nathalie Kontny, Udo González-Neira, Anna Picci, Piero Alonso, Javier Patino-Garcia, Ana Corradini, Nadège Bérard, Perrine Marec Freedman, Neal D. Rothman, Nathaniel Dagnall, Casey L. Burdett, Laurie Jones, Kristine Manning, Michelle Wyatt, Kathleen Zhou, Weiyin Yeager, Meredith Cox, David G. Hoover, Robert N. Khan, Javed Armstrong, Gregory T. Leisenring, Wendy M. Bhatia, Smita Robison, Leslie L. Kulozik, Andreas E. Kriebel, Jennifer Meitinger, Thomas Metzler, Markus Hartmann, Wolfgang Strauch, Konstantin Kirchner, Thomas Dirksen, Uta Morton, Lindsay M. Mirabello, Lisa Tucker, Margaret A. Tirode, Franck Chanock, Stephen J. Delattre, Olivier |
| author_facet | Machiela, Mitchell J. Grünewald, Thomas G. P. Surdez, Didier Reynaud, Stephanie Mirabeau, Olivier Karlins, Eric Rubio, Rebeca Alba Zaidi, Sakina Grossetete-Lalami, Sandrine Ballet, Stelly Lapouble, Eve Laurence, Valérie Michon, Jean Pierron, Gaelle Kovar, Heinrich Gaspar, Nathalie Kontny, Udo González-Neira, Anna Picci, Piero Alonso, Javier Patino-Garcia, Ana Corradini, Nadège Bérard, Perrine Marec Freedman, Neal D. Rothman, Nathaniel Dagnall, Casey L. Burdett, Laurie Jones, Kristine Manning, Michelle Wyatt, Kathleen Zhou, Weiyin Yeager, Meredith Cox, David G. Hoover, Robert N. Khan, Javed Armstrong, Gregory T. Leisenring, Wendy M. Bhatia, Smita Robison, Leslie L. Kulozik, Andreas E. Kriebel, Jennifer Meitinger, Thomas Metzler, Markus Hartmann, Wolfgang Strauch, Konstantin Kirchner, Thomas Dirksen, Uta Morton, Lindsay M. Mirabello, Lisa Tucker, Margaret A. Tirode, Franck Chanock, Stephen J. Delattre, Olivier |
| author_sort | Machiela, Mitchell J. |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-6085378 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2018 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-60853782018-08-13 Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility Machiela, Mitchell J. Grünewald, Thomas G. P. Surdez, Didier Reynaud, Stephanie Mirabeau, Olivier Karlins, Eric Rubio, Rebeca Alba Zaidi, Sakina Grossetete-Lalami, Sandrine Ballet, Stelly Lapouble, Eve Laurence, Valérie Michon, Jean Pierron, Gaelle Kovar, Heinrich Gaspar, Nathalie Kontny, Udo González-Neira, Anna Picci, Piero Alonso, Javier Patino-Garcia, Ana Corradini, Nadège Bérard, Perrine Marec Freedman, Neal D. Rothman, Nathaniel Dagnall, Casey L. Burdett, Laurie Jones, Kristine Manning, Michelle Wyatt, Kathleen Zhou, Weiyin Yeager, Meredith Cox, David G. Hoover, Robert N. Khan, Javed Armstrong, Gregory T. Leisenring, Wendy M. Bhatia, Smita Robison, Leslie L. Kulozik, Andreas E. Kriebel, Jennifer Meitinger, Thomas Metzler, Markus Hartmann, Wolfgang Strauch, Konstantin Kirchner, Thomas Dirksen, Uta Morton, Lindsay M. Mirabello, Lisa Tucker, Margaret A. Tirode, Franck Chanock, Stephen J. Delattre, Olivier Nat Commun Article 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. Nature Publishing Group UK 2018-08-09 /pmc/articles/PMC6085378/ /pubmed/30093639 http://dx.doi.org/10.1038/s41467-018-05537-2 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article Machiela, Mitchell J. Grünewald, Thomas G. P. Surdez, Didier Reynaud, Stephanie Mirabeau, Olivier Karlins, Eric Rubio, Rebeca Alba Zaidi, Sakina Grossetete-Lalami, Sandrine Ballet, Stelly Lapouble, Eve Laurence, Valérie Michon, Jean Pierron, Gaelle Kovar, Heinrich Gaspar, Nathalie Kontny, Udo González-Neira, Anna Picci, Piero Alonso, Javier Patino-Garcia, Ana Corradini, Nadège Bérard, Perrine Marec Freedman, Neal D. Rothman, Nathaniel Dagnall, Casey L. Burdett, Laurie Jones, Kristine Manning, Michelle Wyatt, Kathleen Zhou, Weiyin Yeager, Meredith Cox, David G. Hoover, Robert N. Khan, Javed Armstrong, Gregory T. Leisenring, Wendy M. Bhatia, Smita Robison, Leslie L. Kulozik, Andreas E. Kriebel, Jennifer Meitinger, Thomas Metzler, Markus Hartmann, Wolfgang Strauch, Konstantin Kirchner, Thomas Dirksen, Uta Morton, Lindsay M. Mirabello, Lisa Tucker, Margaret A. Tirode, Franck Chanock, Stephen J. Delattre, Olivier Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility |
| title | Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility |
| title_full | Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility |
| title_fullStr | Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility |
| title_full_unstemmed | Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility |
| title_short | Genome-wide association study identifies multiple new loci associated with Ewing sarcoma susceptibility |
| title_sort | genome-wide association study identifies multiple new loci associated with ewing sarcoma susceptibility |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6085378/ https://www.ncbi.nlm.nih.gov/pubmed/30093639 http://dx.doi.org/10.1038/s41467-018-05537-2 |
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