Diffuse gliomas classified by 1p/19q co-deletion, TERT promoter and IDH mutation status are associated with specific genetic risk loci.
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Date
2018-05-01Author
Labreche, K
Kinnersley, B
Berzero, G
Di Stefano, AL
Rahimian, A
Detrait, I
Marie, Y
Grenier-Boley, B
Hoang-Xuan, K
Delattre, J-Y
Idbaih, A
Houlston, RS
Sanson, M
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Chromosomes, Human, Pair 1
Chromosomes, Human, Pair 19
Humans
Glioma
Brain Neoplasms
Genetic Predisposition to Disease
Isocitrate Dehydrogenase
Telomerase
Proto-Oncogene Proteins c-myc
RNA, Messenger
Case-Control Studies
Mutation
Polymorphism, Single Nucleotide
European Continental Ancestry Group
Stathmin
Promoter Regions, Genetic
Genetic Loci
Genetic Association Studies
Preliminary Data
Research team
Cancer Genomics
Language
eng
Date accepted
2018-02-14
License start date
2018-05
Citation
Acta neuropathologica, 2018, 135 (5), pp. 743 - 755
Publisher
SPRINGER
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
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