Whole-exome mutational landscape of neuroendocrine carcinomas of the gallbladder | |
Liu, Fatao1,2,3,4; Li, Yongsheng2,3,4,5; Ying, Dongjian6; Qiu, Shimei1,2,3,4; He, Yong7; Li, Maolan1,2,4; Liu, Yun2,3,4,5; Zhang, Yijian1,2,3,4; Zhu, Qin1,2,3,4; Hu, Yunping1,2,3,4 | |
刊名 | SIGNAL TRANSDUCTION AND TARGETED THERAPY |
2021-02-10 | |
卷号 | 6 |
ISSN号 | 2095-9907 |
DOI | 10.1038/s41392-020-00412-3 |
通讯作者 | Mu, Jiasheng(mujiasheng@xinhuamed.com.cn) ; Cao, Yang(2316029@zju.edu.cn) ; Liu, Yingbin(laoniulyb@shsmu.edu.cn) |
英文摘要 | Neuroendocrine carcinoma (NEC) of the gallbladder (GB-NEC) is a rare but extremely malignant subtype of gallbladder cancer (GBC). The genetic and molecular signatures of GB-NEC are poorly understood; thus, molecular targeting is currently unavailable. In the present study, we applied whole-exome sequencing (WES) technology to detect gene mutations and predicted somatic single-nucleotide variants (SNVs) in 15 cases of GB-NEC and 22 cases of general GBC. In 15 GB-NECs, the C>T mutation was predominant among the 6 types of SNVs. TP53 showed the highest mutation frequency (73%, 11/15). Compared with neuroendocrine carcinomas of other organs, significantly mutated genes (SMGs) in GB-NECs were more similar to those in pulmonary large-cell neuroendocrine carcinomas (LCNECs), with driver roles for TP53 and RB1. In the COSMIC database of cancer-related genes, 211 genes were mutated. Strikingly, RB1 (4/15, 27%) and NAB2 (3/15, 20%) mutations were found specifically in GB-NECs; in contrast, mutations in 29 genes, including ERBB2 and ERBB3, were identified exclusively in GBC. Mutations in RB1 and NAB2 were significantly related to downregulation of the RB1 and NAB2 proteins, respectively, according to immunohistochemical (IHC) data (p values=0.0453 and 0.0303). Clinically actionable genes indicated 23 mutated genes, including ALK, BRCA1, and BRCA2. In addition, potential somatic SNVs predicted by ISOWN and SomVarIUS constituted 6 primary COSMIC mutation signatures (1, 3, 30, 6, 7, and 13) in GB-NEC. Genes carrying somatic SNVs were enriched mainly in oncogenic signaling pathways involving the Notch, WNT, Hippo, and RTK-RAS pathways. In summary, we have systematically identified the mutation landscape of GB-NEC, and these findings may provide mechanistic insights into the specific pathogenesis of this deadly disease. |
资助项目 | National Natural Science Foundation of China[81902361] ; National Natural Science Foundation of China[31620103910] ; National Natural Science Foundation of China[81874181] ; National Natural Science Foundation of China[91940305] ; National Natural Science Foundation of China[81702381] ; Shanghai Sailing Program[19YF1433000] ; Shanghai Artificial Intelligence Innovation and Development Project[2019-RGZN-01096] ; Medical Science and Technology Project of Zhejiang Provincial Health Commission[2019334001] ; Medical Science and Technology Program of Ningbo[2019Y06] ; Natural Science Foundation of Ningbo[2019A610208] ; Shanghai Key Laboratory of Biliary Tract Disease Research Foundation[17DZ2260200] ; Youth Science and Technology Innovation Studio of Shanghai Jiao Tong University School of Medicine[JYKCGZS04] |
WOS研究方向 | Biochemistry & Molecular Biology ; Cell Biology |
语种 | 英语 |
出版者 | SPRINGERNATURE |
WOS记录号 | WOS:000618772900001 |
资助机构 | National Natural Science Foundation of China ; Shanghai Sailing Program ; Shanghai Artificial Intelligence Innovation and Development Project ; Medical Science and Technology Project of Zhejiang Provincial Health Commission ; Medical Science and Technology Program of Ningbo ; Natural Science Foundation of Ningbo ; Shanghai Key Laboratory of Biliary Tract Disease Research Foundation ; Youth Science and Technology Innovation Studio of Shanghai Jiao Tong University School of Medicine |
内容类型 | 期刊论文 |
源URL | [http://ir.hfcas.ac.cn:8080/handle/334002/120236] |
专题 | 中国科学院合肥物质科学研究院 |
通讯作者 | Mu, Jiasheng; Cao, Yang; Liu, Yingbin |
作者单位 | 1.Shanghai Jiao Tong Univ, Xinhua Hosp, Dept Gen Surg, Sch Med, Shanghai 200092, Peoples R China 2.Shanghai Key Lab Biliary Tract Dis, Shanghai 200092, Peoples R China 3.State Key Lab Oncogenes & Related Genes, Shanghai, Peoples R China 4.Thanghai Res Ctr Biliary Tract Dis, Shanghai 200092, Peoples R China 5.Shanghai Jiao Tong Univ, Dept Biliary Pancreat Surg, Renji Hosp, Shanghai, Peoples R China 6.Lihuili Hosp, Dept Minimal Invas Surg, Ningbo Med Ctr, Ningbo 315040, Zhejiang, Peoples R China 7.Nanchang Univ, Dept Hepatopancreatobiliary Surg, Ganzhou Hosp, Nanchang 341000, Jiangxi, Peoples R China 8.Shanghai Jiao Tong Univ, Dept Pediat Surg, Xinhua Hosp, Sch Med, Shanghai 200092, Peoples R China 9.Shanghai Jiao Tong Univ, Informat & Big Data Ctr, Xinhua Hosp, Sch Med, Shanghai 200092, Peoples R China 10.Zhejiang Univ, Dept Surg, Affiliated Hosp 2, Sch Med, Hangzhou 310009, Zhejiang, Peoples R China |
推荐引用方式 GB/T 7714 | Liu, Fatao,Li, Yongsheng,Ying, Dongjian,et al. Whole-exome mutational landscape of neuroendocrine carcinomas of the gallbladder[J]. SIGNAL TRANSDUCTION AND TARGETED THERAPY,2021,6. |
APA | Liu, Fatao.,Li, Yongsheng.,Ying, Dongjian.,Qiu, Shimei.,He, Yong.,...&Liu, Yingbin.(2021).Whole-exome mutational landscape of neuroendocrine carcinomas of the gallbladder.SIGNAL TRANSDUCTION AND TARGETED THERAPY,6. |
MLA | Liu, Fatao,et al."Whole-exome mutational landscape of neuroendocrine carcinomas of the gallbladder".SIGNAL TRANSDUCTION AND TARGETED THERAPY 6(2021). |
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