Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma.
Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma.
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DOI：
10.1016/j.ccell.2017.07.007
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发表时间：
2017-08-14
期刊：
影响因子：
50.3
通讯作者：
Cancer Genome Atlas Research Network
中科院分区：
文献类型：
--
作者：
Cancer Genome Atlas Research Network. Electronic address: andrew_aguirre@dfci.harvard.edu;Cancer Genome Atlas Research Network
我们对150例胰腺导管腺癌（PDAC）标本进行了整合的基因组、转录组和蛋白质组分析，包括具有特征性低肿瘤细胞构成的样本。深度全外显子组测序揭示了KRAS、TP 53、CDKN 2A、SMAD 4、RNF 43、ARID 1A、TGFβR2、GNAS、RREB 1和PBRM 1中的复发性体细胞突变。KRAS野生型肿瘤包含其他致癌驱动因子的改变，包括GNAS，BRAF，CTNNB 1和其他RAS途径基因。一个肿瘤亚组含有多个KRAS突变，其中一些显示出双等位基因突变的证据。蛋白质谱鉴定了具有低上皮-间质转化和高MTOR通路评分的有利预后子集。还鉴定了非编码RNA与肿瘤特异性mRNA亚型的关联。我们的综合多平台分析揭示了PDAC的复杂分子景观，并为精准医学提供了路线图。这项TCGA研究表明，一些PDAC携带多种KRAS突变，包括双等位基因突变，KRAS野生型PDAC在其他RAS途径基因和其他致癌驱动因子中存在改变，低上皮-间质转化和高MTOR途径评分与良好的预后相关。
We performed integrated genomic, transcriptomic and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1 and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1 and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine. This TCGA study shows that some PDAC carry multiple KRAS mutations, including biallelic mutations, that KRAS wild-type PDAC harbor alterations in other RAS pathway genes and other oncogenic drivers, and that low epithelial-mesenchymal transition and high MTOR pathway scores correlate with a favorable prognosis.
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影响因子：
4.4
作者：
Bibikova, Marina;Barnes, Bret;Shen, Richard
通讯作者：
Shen, Richard
影响因子：
7.3
作者：
Amato, Eliana;dal Molin, Marco;Mafficini, Andrea;Yu, Jun;Malleo, Giuseppe;Rusev, Borislav;Fassan, Matteo;Antonello, Davide;Sadakari, Yoshihiko;Castelli, Paola;Zamboni, Giuseppe;Maitra, Anirban;Salvia, Roberto;Hruban, Ralph H.;Bassi, Claudio;Capelli, Paola;Lawlor, Rita T.;Goggins, Michael;Scarpa, Aldo
通讯作者：
Scarpa, Aldo
影响因子：
64.5
作者：
Cancer Genome Atlas Research Network
通讯作者：
Cancer Genome Atlas Research Network
关于癌症基因组地图集的泛伴奏蛋白质组学观点。
影响因子：
16.6
作者：
Akbani, Rehan;Ng, Patrick Kwok Shing;Werner, Henrica M. J.;Shahmoradgoli, Maria;Zhang, Fan;Ju, Zhenlin;Liu, Wenbin;Yang, Ji-Yeon;Yoshihara, Kosuke;Li, Jun;Ling, Shiyun;Seviour, Elena G.;Ram, Prahlad T.;Minna, John D.;Diao, Lixia;Tong, Pan;Heymach, John V.;Hill, Steven M.;Dondelinger, Frank;Stadler, Nicolas;Byers, Lauren A.;Meric-Bernstam, Funda;Weinstein, John N.;Broom, Bradley M.;Verhaak, Roeland G. W.;Liang, Han;Mukherjee, Sach;Lu, Yiling;Mills, Gordon B.
通讯作者：
Mills, Gordon B.
影响因子：
28.2
作者：
Chen, Shih-Hsun;Zhang, Youyan;Peng, Sheng-Bin
通讯作者：
Peng, Sheng-Bin