来自美国基因泰克公司的Sekar Seshagiri及其同事报道了小细胞肺癌的外显子组、转录组和拷贝变异的相关数据。他们在27%的样本中发现SOX2基因的扩增现象,同时还发现一个复发性的RFL-MYCL1融合现象。相关的研究论文于9月2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】全基因组综合分析鉴定SOX2是小细胞肺癌中频繁扩增的基因

【译文】小细胞肺癌(SCLC)是一种特别地侵入性疾病,预后很差。本研究获得了来自约53个样本(包括36对原发性人SCLC和正常组织)和17个匹配的SCLC和类淋巴母细胞细胞系样本的外显子组、转录组和拷贝变异的相关数据。我们也获得了来自4份原发性肿瘤和23份SCLC细胞系的数据。我们在SCLC中鉴定了22个显著地变异基因,其中包括编码激酶、G蛋白偶联受体和染色质修饰蛋白的基因。我们在SCLC中发现从属SOX基因家族的一些基因存在突变。我们也在约27%的样本中发现SOX2的扩增现象。使用shRNAs抑制SOX2的表达能够阻断的SOX2-扩增的SCLC细胞系的增殖。RNA测序鉴定到多个融合转录本和复发性的RLF-MYCL1融合现象。将发生RLF-MYCL1融合的SCLC细胞系中的MYCL1基因沉默后,导致细胞增殖程度降低。这些数据深入呈现了SCLC中发生的基因变异谱,鉴定了一些用于治疗性干预的潜在靶标。

英文原稿


[Title]: Comprehensive genomic analysis identifies SOX2 as a frequently amplified gene in small-cell lung cancer 

[Authors]: Charles M Rudin, Steffen Durinck, Eric W Stawiski, John T Poirier, Zora Modrusan, David S Shames, Emily A Bergbower, Yinghui Guan, James Shin, Joseph Guillory, Celina Sanchez Rivers, Catherine K Foo, Deepali Bhatt, Jeremy Stinson, Florian Gnad, Peter M Haverty, Robert Gentleman, Subhra Chaudhuri, Vasantharajan Janakiraman, Bijay S Jaiswal, Chaitali Parikh, Wenlin Yuan, Zemin Zhang, Hartmut Koeppen, Thomas D Wu, Howard M Stern, Robert L Yauch, Kenneth E Huffman, Diego D Paskulin, Peter B Illei, Marileila Varella-Garcia, Adi F Gazdar, Frederic J de Sauvage, Richard Bourgon, John D Minna, Malcolm V Brock & Somasekar Seshagiri

[Abstract]: 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.

原文地址

http://www.nature.com/ng/journal/v44/n10/full/ng.2405.html

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