Whole-exome sequencing of alpha-fetoprotein producing gastric carcinoma reveals genomic profile and therapeutic targets.
Whole-exome sequencing of alpha-fetoprotein producing gastric carcinoma reveals genomic profile and therapeutic targets.
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产生甲胎蛋白的胃癌的全外显子组测序揭示了基因组图谱和治疗靶点
DOI：
10.1038/s41467-021-24170-0
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发表时间：
2021-06-24
影响因子：
16.6
通讯作者：
Teng L
中科院分区：
文献类型：
--
作者：
Lu J;Ding Y;Chen Y;Jiang J;Chen Y;Huang Y;Wu M;Li C;Kong M;Zhao W;Wang H;Zhang J;Li Z;Lu Y;Yu X;Jin K;Zhou D;Zhou T;Teng F;Zhang H;Zhou Z;Wang H;Teng L
产生甲胎蛋白的胃癌(AFPGC)是一种罕见的侵袭性胃癌。然而，人们对这种疾病的基因组特征知之甚少。我们对AFPGC进行了全外显子测序分析，发现了34个显著突变的基因。体细胞拷贝数改变分析显示了几个显著的局域扩增(如19q12、17q12)和局域缺失(如1p36.11、9p21.3)，其中一些对患者的预后产生了负面影响。比较分析表明，AFPGC具有与胃癌基因组图谱和四种分子亚型不同的基因组特征。在AFPGC中发现了几个具有潜在治疗靶点的频繁改变的基因。进一步分析表明，在19q12扩增CCNE1和/或在17q12扩增ERBB2的AFPGC的存活率较低，且更具侵袭性。随后，基于我们建立的AFPGC患者来源的异种移植模型，进行了转译研究，并验证了靶向CCNE1和ERBB2的治疗价值。在这项工作中，我们提供了对AFPGC基因组特征的了解，并提出了一个探索和验证基因组指导的个体化治疗该疾病的平台。
Alpha-fetoprotein producing gastric carcinoma (AFPGC) is a rare and aggressive subtype of gastric cancer. However, little is known about the genomic features of this disease. We perform whole-exome sequencing analysis of AFPGC, and identify 34 significantly mutated genes. Somatic copy number alterations analysis reveals several significant focal amplifications (e.g. 19q12, 17q12) and focal deletions (e.g. 1p36.11, 9p21.3), and some of these negatively affect the patient prognosis. Comparative analyses reveal that AFPGC has distinct genomic features from gastric cancer of The Cancer Genome Atlas as well as four molecular subtypes. Several frequently altered genes with potential as therapeutic targets are identified in AFPGC. Further analysis reveals that AFPGC with amplification ofCCNE1at 19q12 and/orERBB2at 17q12 show poorer survival and more aggressive. Subsequently, based on our established patient-derived xenograft models for AFPGC, translational research is performed and the therapeutic value of targetingCCNE1andERBB2is validated. In this work, we provide an understanding of genomic characteristics of AFPGC and propose a platform to explore and validate the genome-guided personalized treatment for this disease.
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染色体不稳定性通过胞质DNA反应驱动转移。
影响因子：
64.8
作者：
Bakhoum SF;Ngo B;Laughney AM;Cavallo JA;Murphy CJ;Ly P;Shah P;Sriram RK;Watkins TBK;Taunk NK;Duran M;Pauli C;Shaw C;Chadalavada K;Rajasekhar VK;Genovese G;Venkatesan S;Birkbak NJ;McGranahan N;Lundquist M;LaPlant Q;Healey JH;Elemento O;Chung CH;Lee NY;Imielenski M;Nanjangud G;Pe'er D;Cleveland DW;Powell SN;Lammerding J;Swanton C;Cantley LC
通讯作者：
Cantley LC
影响因子：
8
作者：
Bullock, AN;Henckel, J;Fersht, AR
通讯作者：
Fersht, AR
DOI：
10.1093/bioinformatics/btv408
发表时间：
2015-11-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Gehring JS;Fischer B;Lawrence M;Huber W
通讯作者：
Huber W
影响因子：
28.5
作者：
Chen Z;Huang W;Tian T;Zang W;Wang J;Liu Z;Li Z;Lai Y;Jiang Z;Gao J;Shen L
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Shen L
影响因子：
8
作者：
Gala K;Li Q;Sinha A;Razavi P;Dorso M;Sanchez-Vega F;Chung YR;Hendrickson R;Hsieh JJ;Berger M;Schultz N;Pastore A;Abdel-Wahab O;Chandarlapaty S
通讯作者：
Chandarlapaty S