2012年8月27日 訊 /生物谷BIOON/ --近日,，來自加利福尼亞大學梅奧診所的研究者通過研究發(fā)現(xiàn)，在遺傳密碼的特殊位置攜帶堿基“G”的人群患特定類型的腦瘤風險是攜帶堿基“A”的人群的6倍以上,。這項研究成果刊登在了8月26日的國際著名雜志Nature Genetics上,。這項研究成果可以幫助研究者快速發(fā)現(xiàn)患有特定神經(jīng)膠質(zhì)瘤的患者，以利于對患者進行早期診斷和治療,。
研究者想確定這種特定位點的堿基置換是否是腦瘤的主要發(fā)病原因,。基于研究發(fā)現(xiàn),，研究者認為臨床檢驗可以確定病人所患的腦瘤類型,。數(shù)年之前，研究者試圖去尋找和神經(jīng)膠質(zhì)瘤發(fā)展相關的基因組區(qū)域,，最終研究者發(fā)現(xiàn)8號染色體的部分包含的單核苷酸多態(tài)性或者SNPs和腦瘤直接相關,。從那時候開始，研究者Jenkins便和同事使用一種復雜的基因組技術來尋找引發(fā)腦瘤形成的特定SNP,。
通過大量的摸索試驗,，研究者發(fā)現(xiàn)了一種SNP，稱為rs55705857（乳腺癌相關基因）也和神經(jīng)膠質(zhì)瘤的發(fā)病相關,，研究者在這個SNP上發(fā)現(xiàn)的是更多的“G”鳥嘌呤,，而不是“A”腺嘌呤,，其和神經(jīng)膠質(zhì)瘤的緩慢發(fā)展直接相關。
與此同時,，研究者也比對了哺乳動物進化過程中的基因突變序列的差異性,，發(fā)現(xiàn)這種突變早在鴨嘴獸中已經(jīng)存在了。計算機模型分析揭示了這種突變的區(qū)域或許是一種microRNA,，microRNA是一種特殊的核酸序列,，可以控制細胞中遺傳信使的活性。結果顯示SNP攜帶有部分的microRNA功能,，而且堿基從A到G的突變會帶來明顯的后果,。研究者目前正在研究是否microRNA真正存在，而且其功能是如何的,？
研究者Jenkins表示,，改變的microRNA或許以腫瘤抑制基因為靶點，其或許可以激活癌基因,，也可以調(diào)節(jié)基因組的穩(wěn)定性,。目前對于基因組新紀元的最大的挑戰(zhàn)就是如何賦予突變基因新的功能。（生物谷Bioon.com）
編譯自：Genomic Variant That Increases Risk of Brain Tumors Discovered
doi:10.1038/ng.2388
PMC:
PMID:
A low-frequency variant at 8q24.21 is strongly associated with risk of oligodendroglial tumors and astrocytomas with IDH1 or IDH2 mutation
Robert B Jenkins,1, 12 Yuanyuan Xiao,2, 11 Hugues Sicotte,3, 11 Paul A Decker,3, 11 Thomas M Kollmeyer,1, 11 Helen M Hansen,4, 11 Matthew L Kosel,3, 11 Shichun Zheng,4 Kyle M Walsh,4, 5 Terri Rice,4 Paige Bracci,2 Lucie S McCoy,4 Ivan Smirnov,4 Joseph S Patoka,4 George Hsuang,4 Joe L Wiemels,2, 6 Tarik Tihan,7 Alexander R Pico,8 Michael D Prados,4 Susan M Chang,4 Mitchel S Berger,4 Alissa A Caron,1 Stephanie R Fink,1 Chandralekha Halder,1 Amanda L Rynearson,1 Brooke L Fridley,3 Jan C Buckner,9 Brian P O'Neill,10 Caterina Giannini,1 Daniel H Lachance,1, 10 John K Wiencke,4, 6, 12 Jeanette E Eckel-Passow3, 12 & Margaret R Wrensch4, 6, 12 et al.
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.
