A novel genomic classification system of gastric cancer via integrating multidimensional genomic characteristics.
A novel genomic classification system of gastric cancer via integrating multidimensional genomic characteristics.
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整合多维基因组特征的新型胃癌基因组分类系统
DOI：
10.1007/s10120-021-01201-9
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Teng L
中科院分区：
文献类型：
--
作者：
Wang H;Ding Y;Chen Y;Jiang J;Chen Y;Lu J;Kong M;Mo F;Huang Y;Zhao W;Fang P;Chen X;Teng X;Xu N;Lu Y;Yu X;Li Z;Zhang J;Wang H;Bao X;Zhou D;Chi Y;Zhou T;Zhou Z;Chen S;Teng L
背景胃癌（gastric cancer，GC）是恶性肿瘤死亡的主要原因之一，具有高度异质性.目前缺乏临床适用的分子分类系统，以指导精准medicine.MethodsA共70例中国GC患者纳入本研究，并进行全外显子测序。进行无监督聚类以基于突变特征、拷贝数变异、新抗原、克隆性和基本基因组改变来鉴定基因组亚组。亚组的特点是由临床病理因素，分子特征，和pregnancy.ResultsWe确定了32个显著突变基因（SMG），包括TP 53，ARID 1A，PIK 3CA，CDH 1，和RHOA。其中PREX 2、PIEZO 1和FSIP 2在GC中未见报道。使用一种新的基于基因组的分类方法，整合多维基因组特征，我们将GC分为四个亚型，具有不同的临床表型和预后。亚型1主要为Lauren肠型，具有复发性TP 53突变和ERBB 2扩增，高肿瘤突变负荷（TMB）/肿瘤新抗原负荷（TNB），瘤内异质性，有肝转移倾向。亚型2易发生于高龄患者，伴有TP 53和SYN E1突变，TMB/TNB高，预后差。亚型3和亚型4包括患者主要弥漫/混合型肿瘤，高频率的腹膜转移，和基因组的稳定性，而亚型4与良好的预后。ConclusionsBy整合多维基因组特征，我们提出了一种新的基因组分类系统的GC与临床表型，并提供了一个新的见解，以促进基因组指导的风险分层和疾病管理。
BackgroundGastric cancer (GC) is one of the leading causes of cancer deaths with high heterogeneity. There is currently a paucity of clinically applicable molecular classification system to guide precise medicine.MethodsA total of 70 Chinese patients with GC were included in this study and whole-exome sequencing was performed. Unsupervised clustering was undertaken to identify genomic subgroups, based on mutational signature, copy number variation, neoantigen, clonality, and essential genomic alterations. Subgroups were characterized by clinicopathological factors, molecular features, and prognosis.ResultsWe identified 32 significantly mutated genes (SMGs), includingTP53, ARID1A, PIK3CA, CDH1,andRHOA. Of these,PREX2, PIEZO1,andFSIP2have not been previously reported in GC. Using a novel genome-based classification method that integrated multidimensional genomic features, we categorized GC into four subtypes with distinct clinical phenotypes and prognosis. Subtype 1, which was predominantly Lauren intestinal type, harbored recurrentTP53mutation andERBB2amplification, high tumor mutation burden (TMB)/tumor neoantigen burden (TNB), and intratumoral heterogeneity, with a liver metastasis tendency. Subtype 2 tended to occur at an elder age, accompanying with frequentTP53andSYNE1mutations, high TMB/TNB, and was associated with poor prognosis. Subtype 3 and subtype 4 included patients with mainly diffuse/mixed type tumors, high frequency of peritoneal metastasis, and genomical stability, whereas subtype 4 was associated with a favorable prognosis.ConclusionsBy integrating multidimensional genomic characteristics, we proposed a novel genomic classification system of GC associated with clinical phenotypes and provided a new insight to facilitate genome-guided risk stratification and disease management.
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影响因子：
29.4
作者：
Boland CR;Goel A
通讯作者：
Goel A
影响因子：
--
作者：
Derks S;Liao X;Chiaravalli AM;Xu X;Camargo MC;Solcia E;Sessa F;Fleitas T;Freeman GJ;Rodig SJ;Rabkin CS;Bass AJ
通讯作者：
Bass AJ
影响因子：
64.8
作者：
Berger, Michael F.;Hodis, Eran;Heffernan, Timothy P.;Deribe, Yonathan Lissanu;Lawrence, Michael S.;Protopopov, Alexei;Ivanova, Elena;Watson, Ian R.;Nickerson, Elizabeth;Ghosh, Papia;Zhang, Hailei;Zeid, Rhamy;Ren, Xiaojia;Cibulskis, Kristian;Sivachenko, Andrey Y.;Wagle, Nikhil;Sucker, Antje;Sougnez, Carrie;Onofrio, Robert;Ambrogio, Lauren;Auclair, Daniel;Fennell, Timothy;Carter, Scott L.;Drier, Yotam;Stojanov, Petar;Singer, Meredith A.;Voet, Douglas;Jing, Rui;Saksena, Gordon;Barretina, Jordi;Ramos, Alex H.;Pugh, Trevor J.;Stransky, Nicolas;Parkin, Melissa;Winckler, Wendy;Mahan, Scott;Ardlie, Kristin;Baldwin, Jennifer;Wargo, Jennifer;Schadendorf, Dirk;Meyerson, Matthew;Gabriel, Stacey B.;Golub, Todd R.;Wagner, Stephan N.;Lander, Eric S.;Getz, Gad;Chin, Lynda;Garraway, Levi A.
通讯作者：
Garraway, Levi A.
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
对胃癌治疗中高温腹膜化疗的随机和高质量非随机研究的30年经验 - A荟萃分析。
DOI：
10.1016/j.ejca.2017.03.030
发表时间：
2017-07
期刊：
European journal of cancer (Oxford, England : 1990)
影响因子：
--
作者：
Desiderio J;Chao J;Melstrom L;Warner S;Tozzi F;Fong Y;Parisi A;Woo Y
通讯作者：
Woo Y