来自美国梅奥临床医学院的Robert Jenkins及其同事报道了8q24.21上胶质瘤风险区域的精细定位图。他们在该区域新鉴定到一些低频率的突变,这个区域与少枝胶质肿瘤和IDH1IDH2基因突变的星形细胞瘤密切相关。相关的研究论文于8月26日在线发表在《Nature Genetics》期刊上。

-2012年10月《自然-遗传》

中文翻译


【题目】首次发现DNA非编码区与癌症风险强关联 

【译文】已有研究表明8q24.21上的突变与神经胶质瘤的发展相关。借助标签单核苷酸多态性(SNP)基因型分型和归责原则,使用长片段PCR合并下一代测序数据并经随后的SNP基因型分型验证,本研究组在8q24.21上鉴定到7个低频率的、与神经胶质瘤密切相关(P = 1 × 10−25~1 × 10−14)的SNPs。在其它六个最高SNPs和两个先前已报道的SNPs经单独调整后,最密切相关的SNP——rs55705857仍保持高度显著性。根据组织学和肿瘤的基因亚型进行分层后,rs55705857与少枝胶质肿瘤和IDH1IDH2基因突变的神经胶质瘤最密切相关(优势率(OR) = 5.1, P = 1.1 × 10−31;OR = 4.8, P = 6.6 × 10−22)。本研究在IDH1IDH2基因突变(2-4级)(OR = 5.16–6.66, P = 4.7 × 10−12 ~2.2 × 10−8)的星形胶质瘤中发现了密切关联的SNP,但未在野生型IDH1IDH2基因的星形胶质瘤中发现。包括rs55705857的保守序列区一直是microRNA的作用模型。

英文原稿


[Title]: A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation

[Authors]: Robert B Jenkins, Yuanyuan Xiao, Hugues Sicotte, Paul A Decker, Thomas M Kollmeyer, Helen M Hansen, Matthew L Kosel, Shichun Zheng, Kyle M Walsh, Terri Rice, Paige Bracci, Lucie S McCoy, Ivan Smirnov, Joseph S Patoka, George Hsuang, Joe L Wiemels, Tarik Tihan, Alexander R Pico, Michael D Prados, Susan M Chang, Mitchel S Berger, Alissa A Caron, Stephanie R Fink, Chandralekha Halder, Amanda L Rynearson, Brooke L Fridley, Jan C Buckner, Brian P O’Neill, Caterina Giannini, Daniel H Lachance, John K Wiencke, Jeanette E Eckel-Passow & Margaret R Wrensch

[Abstract]: Variants at 8q24.21 have been shown to be associated with glioma development. By means of tag SNP genotyping and imputation, pooled next-generation sequencing using long-range PCR and subsequent validation SNP genotyping, we identified seven low-frequency SNPs at 8q24.21 that were strongly associated with glioma risk (P = 1 × 10−25 to 1 × 10−14). The most strongly associated SNP, rs55705857, remained highly significant after individual adjustment for the other top six SNPs and two previously published SNPs. After stratifying by histological and tumor genetic subtype, the most significant associations of rs55705857 were with oligodendroglial tumors and gliomas with mutant IDH1 or IDH2 (odds ratio (OR) = 5.1, P = 1.1 × 10−31 and OR = 4.8, P = 6.6 × 10−22, respectively). Strong associations were observed for astrocytomas with mutated IDH1 or IDH2 (grades 2–4) (OR = 5.16–6.66, P = 4.7 × 10−12 to 2.2 × 10−8) but not for astrocytomas with wild-type IDH1 and IDH2 (smallest P = 0.26). The conserved sequence block that includes rs55705857 is consistently modeled as a microRNA.

原文地址

http://www.nature.com/ng/journal/v44/n10/full/ng.2388.html

本站声明: 生物文库所有文章欢迎转载,所有文章未说明,均属于原创,转载均请注明出处。
本文链接: http://www.bioku.cn/201212/nature-genetics-glioma-single-nucleotide-polymorphism-genotyping/
版权所有: 生物文库 - 生物医学、生物技术核心期刊文摘

留言


八 × = 16


沪ICP备12028140号
点击这里给我发消息   点击这里给我发消息