Integrated exome and transcriptome sequencing reveals ZAK isoform usage in gastric cancer.
Integrated exome and transcriptome sequencing reveals ZAK isoform usage in gastric cancer.
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DOI：
10.1038/ncomms4830
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发表时间：
2014-05-08
影响因子：
16.6
通讯作者：
Zhang, Zemin
中科院分区：
文献类型：
--
作者：
Liu, Jinfeng;McCleland, Mark;Stawiski, Eric W.;Gnad, Florian;Mayba, Oleg;Haverty, Peter M.;Durinck, Steffen;Chen, Ying-Jiun;Klijn, Christiaan;Jhunjhunwala, Suchit;Lawrence, Michael;Liu, Hanbin;Wan, Yinan;Chopra, Vivek;Yaylaoglu, Murat B.;Yuan, Wenlin;Ha, Connie;Gilbert, Houston N.;Reeder, Jens;Pau, Gregoire;Stinson, Jeremy;Stern, Howard M.;Manning, Gerard;Wu, Thomas D.;Neve, Richard M.;de Sauvage, Frederic J.;Modrusan, Zora;Seshagiri, Somasekar;Firestein, Ron;Zhang, Zemin
胃癌是全球癌症死亡率的第二大原因，但对潜在的基因组改变仍知之甚少。在这里，我们进行外显子组和转录组测序和SNP阵列分析，以表征51个原发性胃肿瘤和32个细胞系。对外显子组数据和先前发表的数据集的荟萃分析揭示了微卫星稳定（MSS）肿瘤中的24个显著突变基因和微卫星不稳定（MSI）肿瘤中的16个显著突变基因。我们收集的患者中有一半以上可能从靶向治疗中受益。我们确定了55个剪接位点突变伴随异常剪接产物，除了突变独立的差异异构体在肿瘤中的使用。相对于正常样品，ZAK激酶亚型TV1在胃肿瘤和细胞系中优先上调。在结直肠癌、膀胱癌和乳腺癌中也观察到这种模式。这种特殊亚型的过表达激活了多种癌症相关的转录因子报告基因，而胃细胞系中ZAK的缺失抑制了增殖。这些结果揭示了胃癌中基因组和转录组改变的谱，并鉴定了ZAK的亚型特异性致癌特性。 胃癌是世界上第四大常见癌症，其遗传基础仍然知之甚少。在这里，作者对原发性胃肿瘤和细胞系的外显子组和转录组进行测序和分析，并鉴定出可能在胃癌中具有致癌作用的ZAK激酶亚型。
Gastric cancer is the second leading cause of worldwide cancer mortality, yet the underlying genomic alterations remain poorly understood. Here we perform exome and transcriptome sequencing and SNP array assays to characterize 51 primary gastric tumours and 32 cell lines. Meta-analysis of exome data and previously published data sets reveals 24 significantly mutated genes in microsatellite stable (MSS) tumours and 16 in microsatellite instable (MSI) tumours. Over half the patients in our collection could potentially benefit from targeted therapies. We identify 55 splice site mutations accompanied by aberrant splicing products, in addition to mutation-independent differential isoform usage in tumours. ZAK kinase isoform TV1 is preferentially upregulated in gastric tumours and cell lines relative to normal samples. This pattern is also observed in colorectal, bladder and breast cancers. Overexpression of this particular isoform activates multiple cancer-related transcription factor reporters, while depletion of ZAK in gastric cell lines inhibits proliferation. These results reveal the spectrum of genomic and transcriptomic alterations in gastric cancer, and identify isoform-specific oncogenic properties of ZAK. The genetic basis of gastric cancer, the fourth most common cancer worldwide, remains poorly understood. Here, the authors sequence and analyse the exomes and transcriptomes of primary gastric tumours and cell lines, and identify a ZAK kinase isoform that may have an oncogenic role in gastric cancer.
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DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
28.2
作者：
Bose R;Kavuri SM;Searleman AC;Shen W;Shen D;Koboldt DC;Monsey J;Goel N;Aronson AB;Li S;Ma CX;Ding L;Mardis ER;Ellis MJ
通讯作者：
Ellis MJ
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
9.7
作者：
Liang, Han;Kim, Yon Hui
通讯作者：
Kim, Yon Hui
影响因子：
14.9
作者：
Forbes SA;Bindal N;Bamford S;Cole C;Kok CY;Beare D;Jia M;Shepherd R;Leung K;Menzies A;Teague JW;Campbell PJ;Stratton MR;Futreal PA
通讯作者：
Futreal PA