2012年9月6日 訊 /生物谷BIOON/ --近日，科學(xué)家們已經(jīng)完成了一種致命肺癌類型全面基因突變掃描,。約翰霍普金斯大學(xué)Kimmel癌癥中心科學(xué)家發(fā)現(xiàn)一個名為SOX2的早期胚胎發(fā)育相關(guān)基因在小細(xì)胞肺癌中發(fā)生了突變,。
約翰霍普金斯大學(xué)Kimmel癌癥中心腫瘤學(xué)教授Charles Rudin醫(yī)學(xué)博士說：小細(xì)胞肺癌被診斷發(fā)現(xiàn)時，大部分患者基本都處于晚期,，癌細(xì)胞已經(jīng)擴(kuò)散,，診斷后患者存活的時間不足一年?？茖W(xué)家們發(fā)現(xiàn),，在小細(xì)胞肺癌樣本中，SOX2基因的拷貝數(shù)增加了約27％,。由SOX2基因編碼產(chǎn)生的過剩蛋白質(zhì)可能在促進(jìn)和維持肺細(xì)胞的異常生長中發(fā)揮作用,。
SOX2或許是科學(xué)家們開發(fā)新的靶向藥物來對付這種棘手類型癌癥的一大潛在靶點(diǎn)。在這項(xiàng)發(fā)表在Nature Genetics雜志上的研究中,，約翰霍普金斯大學(xué)與美國德州大學(xué)西南醫(yī)學(xué)中心和美國科羅拉多大學(xué)癌癥中心的工作人員掃描63例非小細(xì)胞肺癌患者的基因組編碼區(qū),。他們發(fā)現(xiàn)基因SOX2在約27％的檢測樣品（56個樣本中有15個）是擴(kuò)增的。
SOX2編碼能結(jié)合DNA的蛋白質(zhì)復(fù)合體,，并控制基因何時以及如何被解碼以生成其他蛋白質(zhì),。SOX2與胚胎干細(xì)胞的組織和器官發(fā)育相關(guān),。在一組110例小細(xì)胞肺癌中,，科學(xué)家們證實(shí)SOX2確實(shí)是表達(dá)增加的。他們發(fā)現(xiàn),，SOX2蛋白過量導(dǎo)致細(xì)胞過度生長引發(fā)癌癥,。這項(xiàng)基因組學(xué)研究可能有助于確定哪些遺傳基因途徑在這種疾病的發(fā)病中發(fā)揮作用，并給研究人員開發(fā)新的治療藥物帶來新思路,。（生物谷：Bioon.com）
doi:10.1038/ng.2405
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Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer
Charles M Rudin,Steffen Durinck,Eric W Stawiski,John T Poirier,Zora Modrusan,David S Shames,Emily A Bergbower,et al.
Small-cell lung cancer (SCLC) is an exceptionally aggressive disease with poor prognosis. Here, we obtained exome, transcriptome and copy-number alteration data from approximately 53 samples consisting of 36 primary human SCLC and normal tissue pairs and 17 matched SCLC and lymphoblastoid cell lines. We also obtained data for 4 primary tumors and 23 SCLC cell lines. We identified 22 significantly mutated genes in SCLC, including genes encoding kinases, G protein–coupled receptors and chromatin-modifying proteins. We found that several members of the SOX family of genes were mutated in SCLC. We also found SOX2 amplification in ~27% of the samples. Suppression of SOX2 using shRNAs blocked proliferation of SOX2-amplified SCLC lines. RNA sequencing identified multiple fusion transcripts and a recurrent RLF-MYCL1 fusion. Silencing of MYCL1 in SCLC cell lines that had the RLF-MYCL1 fusion decreased cell proliferation. These data provide an in-depth view of the spectrum of genomic alterations in SCLC and identify several potential targets for therapeutic intervention.
