A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation.
A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation.
复制标题
DOI：
10.1038/ng.2388
复制
发表时间：
2012-10
期刊：
影响因子：
30.8
通讯作者：
Wrensch, Margaret R.
中科院分区：
文献类型：
--
作者：
Jenkins, Robert B.;Xiao, Yuanyuan;Sicotte, Hugues;Decker, Paul A.;Kollmeyer, Thomas M.;Hansen, Helen M.;Kosel, Matthew L.;Zheng, Shichun;Walsh, Kyle M.;Rice, Terri;Bracci, Paige;McCoy, Lucie S.;Smirnov, Ivan;Patoka, Joseph S.;Hsuang, George;Wiemels, Joe L.;Tihan, Tarik;Pico, Alexander R.;Prados, Michael D.;Chang, Susan M.;Berger, Mitchel S.;Caron, Alissa A.;Fink, Stephanie R.;Halder, Chandralekha;Rynearson, Amanda L.;Fridley, Brooke L.;Buckner, Jan C.;O'Neill, Brian P.;Giannini, Caterina;Lachance, Daniel H.;Wiencke, John K.;Eckel-Passow, Jeanette E.;Wrensch, Margaret R.
映射到 8q24.21 的 SNP 已被证明与神经胶质瘤的发展相关。通过标签 SNP 基因分型/插补、使用长程 PCR 的汇集下一代测序 (NGS) 以及随后的 SNP 基因分型验证，我们确定了 7 个与神经胶质瘤风险一致且高度相关的低频 SNP（p=10−25 至 10−14）。在对其他前六名和两个先前发布的 SNP 进行单独调整后，最相关的 SNP rs55705857 仍然非常显着。按组织学和肿瘤遗传亚型分层后，最显着的关联是少突胶质细胞肿瘤和 IDH1 或 IDH2 突变神经胶质瘤（分别为 ORrs55705857 = 5.1，p=1.1x10−31 和 ORrs55705857 = 4.8，p=6.6 x10−22）。观察到 IDH1 或 IDH2 突变星形细胞瘤（II-IV 级）（OR rs55705857=5.16-6.66；p=4.7x10−12 至 2.2x10−8）有很强的相关性，但 IDH1 或 IDH2 野生型星形细胞瘤没有（最小 p=0.26）。包含 rs55705857 的保守序列块始终被建模为 microRNA。
SNPs mapped to 8q24.21 have been shown to be associated with glioma development. By means of tag SNP genotyping/imputation, pooled next-generation sequencing (NGS) using long-range PCR, and subsequent validation SNP genotyping we identified seven low-frequency SNPs that were consistently and highly associated with glioma risk (p=10−25 to 10−14). The most associated SNP, rs55705857, remained highly significant after individual adjustment for the other top six and two previously published SNPs. After stratifying by histologic and tumor genetic subtype, the most significant associations were with oligodendroglial tumors and IDH1 or IDH2 mutated gliomas, (ORrs55705857 = 5.1, p=1.1x10−31 and ORrs55705857 = 4.8, p=6.6 x10−22, respectively). Strong associations were observed for IDH1 or IDH2 mutated astrocytomas (grades II–IV) (OR rs55705857=5.16–6.66; p=4.7x10−12 to 2.2x10−8), but not IDH1 or IDH2 wild-type astrocytomas (smallest p=0.26). The conserved sequence block that includes rs55705857 is consistently modeled as a microRNA.
登录
查看更多内容
影响因子：
30.8
作者：
Shete S;Hosking FJ;Robertson LB;Dobbins SE;Sanson M;Malmer B;Simon M;Marie Y;Boisselier B;Delattre JY;Hoang-Xuan K;El Hallani S;Idbaih A;Zelenika D;Andersson U;Henriksson R;Bergenheim AT;Feychting M;Lönn S;Ahlbom A;Schramm J;Linnebank M;Hemminki K;Kumar R;Hepworth SJ;Price A;Armstrong G;Liu Y;Gu X;Yu R;Lau C;Schoemaker M;Muir K;Swerdlow A;Lathrop M;Bondy M;Houlston RS
通讯作者：
Houlston RS
影响因子：
3.7
作者：
Low SK;Kuchiba A;Zembutsu H;Saito A;Takahashi A;Kubo M;Daigo Y;Kamatani N;Chiku S;Totsuka H;Ohnami S;Hirose H;Shimada K;Okusaka T;Yoshida T;Nakamura Y;Sakamoto H
通讯作者：
Sakamoto H
影响因子：
12.7
作者：
Hartmann, Christian;Meyer, Jochen;von Deimling, Andreas
通讯作者：
von Deimling, Andreas
影响因子：
64.8
作者：
Lu, Chao;Ward, Patrick S.;Kapoor, Gurpreet S.;Rohle, Dan;Turcan, Sevin;Abdel-Wahab, Omar;Edwards, Christopher R.;Khanin, Raya;Figueroa, Maria E.;Melnick, Ari;Wellen, Kathryn E.;O'Rourke, Donald M.;Berger, Shelley L.;Chan, Timothy A.;Levine, Ross L.;Mellinghoff, Ingo K.;Thompson, Craig B.
通讯作者：
Thompson, Craig B.
影响因子：
30.8
作者：
通讯作者：
--