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Diffuse gliomas classified by 1p/19q co-deletion, TERT promoter and IDH mutation status are associated with specific genetic risk loci

Recent genome-wide association studies of glioma have led to the discovery of single nucleotide polymorphisms (SNPs) at 25 loci influencing risk. Gliomas are heterogeneous, hence to investigate the relationship between risk SNPs and glioma subtype we analysed 1659 tumours profiled for IDH mutation,...

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Autores principales: Labreche, Karim, Kinnersley, Ben, Berzero, Giulia, Di Stefano, Anna Luisa, Rahimian, Amithys, Detrait, Ines, Marie, Yannick, Grenier-Boley, Benjamin, Hoang-Xuan, Khe, Delattre, Jean-Yves, Idbaih, Ahmed, Houlston, Richard S., Sanson, Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904227/
https://www.ncbi.nlm.nih.gov/pubmed/29460007
http://dx.doi.org/10.1007/s00401-018-1825-z
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author Labreche, Karim
Kinnersley, Ben
Berzero, Giulia
Di Stefano, Anna Luisa
Rahimian, Amithys
Detrait, Ines
Marie, Yannick
Grenier-Boley, Benjamin
Hoang-Xuan, Khe
Delattre, Jean-Yves
Idbaih, Ahmed
Houlston, Richard S.
Sanson, Marc
author_facet Labreche, Karim
Kinnersley, Ben
Berzero, Giulia
Di Stefano, Anna Luisa
Rahimian, Amithys
Detrait, Ines
Marie, Yannick
Grenier-Boley, Benjamin
Hoang-Xuan, Khe
Delattre, Jean-Yves
Idbaih, Ahmed
Houlston, Richard S.
Sanson, Marc
author_sort Labreche, Karim
collection PubMed
description Recent genome-wide association studies of glioma have led to the discovery of single nucleotide polymorphisms (SNPs) at 25 loci influencing risk. Gliomas are heterogeneous, hence to investigate the relationship between risk SNPs and glioma subtype we analysed 1659 tumours profiled for IDH mutation, TERT promoter mutation and 1p/19q co-deletion. These data allowed definition of five molecular subgroups of glioma: triple-positive (IDH mutated, 1p/19q co-deletion, TERT promoter mutated); TERT-IDH (IDH mutated, TERT promoter mutated, 1p/19q-wild-type); IDH-only (IDH mutated, 1p/19q wild-type, TERT promoter wild-type); triple-negative (IDH wild-type, 1p/19q wild-type, TERT promoter wild-type) and TERT-only (TERT promoter mutated, IDH wild-type, 1p/19q wild-type). Most glioma risk loci showed subtype specificity: (1) the 8q24.21 SNP for triple-positive glioma; (2) 5p15.33, 9p21.3, 17p13.1 and 20q13.33 SNPs for TERT-only glioma; (3) 1q44, 2q33.3, 3p14.1, 11q21, 11q23.3, 14q12, and 15q24.2 SNPs for IDH mutated glioma. To link risk SNPs to target candidate genes we analysed Hi-C and gene expression data, highlighting the potential role of IDH1 at 2q33.3, MYC at 8q24.21 and STMN3 at 20q13.33. Our observations provide further insight into the nature of susceptibility to glioma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-018-1825-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-59042272018-04-24 Diffuse gliomas classified by 1p/19q co-deletion, TERT promoter and IDH mutation status are associated with specific genetic risk loci Labreche, Karim Kinnersley, Ben Berzero, Giulia Di Stefano, Anna Luisa Rahimian, Amithys Detrait, Ines Marie, Yannick Grenier-Boley, Benjamin Hoang-Xuan, Khe Delattre, Jean-Yves Idbaih, Ahmed Houlston, Richard S. Sanson, Marc Acta Neuropathol Original Paper Recent genome-wide association studies of glioma have led to the discovery of single nucleotide polymorphisms (SNPs) at 25 loci influencing risk. Gliomas are heterogeneous, hence to investigate the relationship between risk SNPs and glioma subtype we analysed 1659 tumours profiled for IDH mutation, TERT promoter mutation and 1p/19q co-deletion. These data allowed definition of five molecular subgroups of glioma: triple-positive (IDH mutated, 1p/19q co-deletion, TERT promoter mutated); TERT-IDH (IDH mutated, TERT promoter mutated, 1p/19q-wild-type); IDH-only (IDH mutated, 1p/19q wild-type, TERT promoter wild-type); triple-negative (IDH wild-type, 1p/19q wild-type, TERT promoter wild-type) and TERT-only (TERT promoter mutated, IDH wild-type, 1p/19q wild-type). Most glioma risk loci showed subtype specificity: (1) the 8q24.21 SNP for triple-positive glioma; (2) 5p15.33, 9p21.3, 17p13.1 and 20q13.33 SNPs for TERT-only glioma; (3) 1q44, 2q33.3, 3p14.1, 11q21, 11q23.3, 14q12, and 15q24.2 SNPs for IDH mutated glioma. To link risk SNPs to target candidate genes we analysed Hi-C and gene expression data, highlighting the potential role of IDH1 at 2q33.3, MYC at 8q24.21 and STMN3 at 20q13.33. Our observations provide further insight into the nature of susceptibility to glioma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-018-1825-z) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2018-02-19 2018 /pmc/articles/PMC5904227/ /pubmed/29460007 http://dx.doi.org/10.1007/s00401-018-1825-z Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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.
spellingShingle Original Paper
Labreche, Karim
Kinnersley, Ben
Berzero, Giulia
Di Stefano, Anna Luisa
Rahimian, Amithys
Detrait, Ines
Marie, Yannick
Grenier-Boley, Benjamin
Hoang-Xuan, Khe
Delattre, Jean-Yves
Idbaih, Ahmed
Houlston, Richard S.
Sanson, Marc
Diffuse gliomas classified by 1p/19q co-deletion, TERT promoter and IDH mutation status are associated with specific genetic risk loci
title Diffuse gliomas classified by 1p/19q co-deletion, TERT promoter and IDH mutation status are associated with specific genetic risk loci
title_full Diffuse gliomas classified by 1p/19q co-deletion, TERT promoter and IDH mutation status are associated with specific genetic risk loci
title_fullStr Diffuse gliomas classified by 1p/19q co-deletion, TERT promoter and IDH mutation status are associated with specific genetic risk loci
title_full_unstemmed Diffuse gliomas classified by 1p/19q co-deletion, TERT promoter and IDH mutation status are associated with specific genetic risk loci
title_short Diffuse gliomas classified by 1p/19q co-deletion, TERT promoter and IDH mutation status are associated with specific genetic risk loci
title_sort diffuse gliomas classified by 1p/19q co-deletion, tert promoter and idh mutation status are associated with specific genetic risk loci
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904227/
https://www.ncbi.nlm.nih.gov/pubmed/29460007
http://dx.doi.org/10.1007/s00401-018-1825-z
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