美國加州大學(xué)洛杉磯分校瓊森綜合癌癥研究中心的科學(xué)家在1月29日的《公共科學(xué)圖書館·遺傳學(xué)》?？习l(fā)表論文指出，他們首次完成了腦癌細(xì)胞系全基因組測序,，這也是截至目前對單個(gè)癌癥細(xì)胞系所做的最為徹底的測序分析,。通過使用最新技術(shù)，此項(xiàng)測序工作得以在一個(gè)月內(nèi)完成,，測序成本大約為3.5萬美元,。
此項(xiàng)研究成果在朝向基于單個(gè)癌癥之獨(dú)特生物學(xué)簽名的個(gè)性化治療方面邁出了新的一步，其所揭示的新分子靶標(biāo)將有助于開發(fā)出更具效力和更少毒性的藥物,。此項(xiàng)研究對于更好地找到監(jiān)測腦癌復(fù)發(fā)的新方法也大有助益,，便于醫(yī)生更早地對腦癌的復(fù)發(fā)做出診斷和治療。借助此項(xiàng)發(fā)現(xiàn),，臨床醫(yī)生還可測定腦癌細(xì)胞被滅活的準(zhǔn)確時(shí)間,，以防止過度使用藥物對人體健康造成的損害。
測序工作是在名為U87的成膠質(zhì)瘤細(xì)胞系上完成的,，在全世界范圍內(nèi)有超過1000個(gè)實(shí)驗(yàn)室正在使用U87細(xì)胞系開展研究,。之所以選擇該細(xì)胞系，是因?yàn)槟壳皩ζ涞难芯孔顬槌浞?。此?xiàng)測序工作將使那些從事細(xì)胞系研究的科學(xué)家們對他們的研究發(fā)現(xiàn)重新進(jìn)行闡述,，并促使他們提出新的前進(jìn)方向。
此次測序工作揭示了幾乎所有潛在的致癌染色體易位及導(dǎo)致該癌癥發(fā)展的基因缺失和突變,。研究人員從細(xì)胞系中取出遺傳物質(zhì)的長鏈,，然后隨機(jī)地將其截?cái)唷Ｔ摪┌Y的數(shù)十億個(gè)不同的DNA片段可由新一代測序技術(shù)同時(shí)進(jìn)行讀取,，遺傳物質(zhì)經(jīng)由10億次以上的分析后就可確保結(jié)果具有高靈敏度和精確度,。
研究人員表示，此一特殊的信息化工具使用了目前最為先進(jìn)的技術(shù),，將大大提高基因分析工作的成效,。以前，科學(xué)家無法了解發(fā)生在一個(gè)癌癥中的大部分突變,，因?yàn)樗鼈兪强床灰姷模F(xiàn)在,，這項(xiàng)新技術(shù)將允許科學(xué)家們監(jiān)視每一種癌癥,，并對其基因組進(jìn)行完全解碼，如此科學(xué)家們就不會(huì)錯(cuò)失任何一個(gè)致癌突變,。
知道了是哪些基因發(fā)生了突變并驅(qū)動(dòng)了癌癥的發(fā)展,，臨床醫(yī)生就能選擇最適于攻擊癌癥特定分子簽名的療法，從而給患者提供更有效的治療,。該測序工作還可展現(xiàn)出驅(qū)動(dòng)癌癥發(fā)展的分子異常,，揭示出的靶標(biāo)或?qū)⒂兄陂_發(fā)出只針對癌細(xì)胞進(jìn)行攻擊同時(shí)又不損害健康細(xì)胞的新療法。
研究人員還指出,，有了癌癥全基因測序圖,，科學(xué)家們就能開發(fā)出靈敏的分子檢測儀,，尋找僅可在癌細(xì)胞內(nèi)發(fā)現(xiàn)的一個(gè)獨(dú)特的基因突變。只要檢測到此一突變即可判定癌癥已復(fù)發(fā),，由此,，患者就能在癌癥復(fù)發(fā)的最早階段得到積極治療。反過來,，這種檢測方法也可用以判定癌癥是否已被有效消除,，從而及時(shí)中止有害人體的治療手段。（生物谷Bioon.com）
癌癥基因組研究：
Nature：美科學(xué)家首次測序癌癥患者基因組
Nature：肺癌和皮膚癌完整基因圖譜測序成功
Nature：基因組和轉(zhuǎn)錄組隨腫瘤轉(zhuǎn)移所發(fā)生的變化
Nature Genetics：迄今規(guī)模最大的罕見腫瘤基因研究完成
生物谷推薦原始出處：
PLoS Genet 6(1): e1000832. doi:10.1371/journal.pgen.1000832
U87MG Decoded: The Genomic Sequence of a Cytogenetically Aberrant Human Cancer Cell Line
Michael James Clark1#, Nils Homer1,2#, Brian D. O'Connor1#, Zugen Chen1#, Ascia Eskin1, Hane Lee1, Barry Merriman1, Stanley F. Nelson1*
1 Department of Human Genetics, University of California Los Angeles, Los Angeles, California, United States of America, 2 Department of Computer Science, University of California Los Angeles, Los Angeles, California, United States of America
U87MG is a commonly studied grade IV glioma cell line that has been analyzed in at least 1,700 publications over four decades. In order to comprehensively characterize the genome of this cell line and to serve as a model of broad cancer genome sequencing, we have generated greater than 30× genomic sequence coverage using a novel 50-base mate paired strategy with a 1.4kb mean insert library. A total of 1,014,984,286 mate-end and 120,691,623 single-end two-base encoded reads were generated from five slides. All data were aligned using a custom designed tool called BFAST, allowing optimal color space read alignment and accurate identification of DNA variants. The aligned sequence reads and mate-pair information identified 35 interchromosomal translocation events, 1,315 structural variations (>100 bp), 191,743 small (<21 bp) insertions and deletions (indels), and 2,384,470 single nucleotide variations (SNVs). Among these observations, the known homozygous mutation in PTEN was robustly identified, and genes involved in cell adhesion were overrepresented in the mutated gene list. Data were compared to 219,187 heterozygous single nucleotide polymorphisms assayed by Illumina 1M Duo genotyping array to assess accuracy: 93.83% of all SNPs were reliably detected at filtering thresholds that yield greater than 99.99% sequence accuracy. Protein coding sequences were disrupted predominantly in this cancer cell line due to small indels, large deletions, and translocations. In total, 512 genes were homozygously mutated, including 154 by SNVs, 178 by small indels, 145 by large microdeletions, and 35 by interchromosomal translocations to reveal a highly mutated cell line genome. Of the small homozygously mutated variants, 8 SNVs and 99 indels were novel events not present in dbSNP. These data demonstrate that routine generation of broad cancer genome sequence is possible outside of genome centers. The sequence analysis of U87MG provides an unparalleled level of mutational resolution compared to any cell line to date.
