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.

最近的神经胶质瘤全基因组关联研究发现了影响风险的 25 个位点的单核苷酸多态性 (SNP)。神经胶质瘤具有异质性，因此为了研究风险 SNP 与神经胶质瘤亚型之间的关系，我们分析了 1659 个肿瘤的 IDH 突变、TERT启动子突变和 1p/19q 共缺失。这些数据可以定义神经胶质瘤的五个分子亚组：三阳性（IDH 突变、1p/19q 共缺失、TERT启动子突变）；TERT -IDH (IDH 突变，TERT启动子突变，1p/19q-野生型)；仅 IDH（IDH 突变、1p/19q 野生型、TERT启动子野生型）；三阴性（IDH 野生型、1p/19q 野生型、TERT启动子野生型）和仅TERT（TERT启动子突变、IDH 野生型、1p/19q 野生型）。大多数胶质瘤风险位点表现出亚型特异性：（1）三阳性胶质瘤的8q24.21 SNP；(2) 仅TERT神经胶质瘤的 5p15.33、9p21.3、17p13.1 和 20q13.33 SNP ；(3) IDH 突变神经胶质瘤的 1q44、2q33.3、3p14.1、11q21、11q23.3、14q12 和 15q24.2 SNP。为了将风险 SNP 与目标候选基因联系起来，我们分析了 Hi-C 和基因表达数据，强调了2q33.3 处的IDH1、8q24.21处的MYC和20q13.33 处的STMN3的潜在作用。我们的观察进一步了解了神经胶质瘤易感性的本质。