Whole-exome mutational landscape of neuroendocrine carcinomas of the gallbladder
作者机构：Department of General SurgeryXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineYangpu DistrictShanghai 200092China Shanghai Key Laboratory of Biliary Tract DiseaseYangpu DistrictShanghai 200092China State Key Laboratory of Oncogenes and Related GenesShanghaiChina Shanghai Research Center of Biliary Tract DiseaseYangpu DistrictShanghai 200092China Department of Biliary-Pancreatic SurgeryRenji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Minimal Invasive SurgeryNingbo Medical Center Lihuili HospitalNingboZhejiang 315040China Department of hepatopancreatobiliary surgeryGanzhou hospital affiliated to Nanchang universityJiangxi 341000China Department of Pediatric SurgeryXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineYangpu DistrictShanghai 200092China Information and Big Data CenterXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineYangpu DistrictShanghai 200092China Department of SurgerySecond Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang 310009China Department of Gastric SurgeryCancer Hospital of the University of Chinese Academy of SciencesHangzhouZhejiang 310022China
出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)
年 卷 期：2021年第6卷第3期
页 面：897-908页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学]
基 金：supported by the National Natural Science Foundation of China(Nos.81902361,31620103910,81874181,91940305,and 81702381) the Shanghai Sailing Program(19YF1433000) the Shanghai Artificial Intelligence Innovation and Development Project(2019-RGZN-01096) the Medical Science and Technology Project of Zhejiang Provincial Health Commission(No.2019334001) the Medical Science and Technology Program of Ningbo(No.2019Y06) the Natural Science Foundation of Ningbo(No.2019A610208) the Shanghai Key Laboratory of Biliary Tract Disease Research Foundation(17DZ2260200) appreciate the support from the Youth Science and Technology Innovation Studio of Shanghai Jiao Tong University School of Medicine(JYKCGZS04).
主 题：gallbladder carcinomas organs
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.Inthe present study,we applied whole-exome sequencing(WES)technology to detect gene mutations and predicted somatic singlenucleotide variants(SNVs)in 15 cases of GB-NEC and 22 cases of general GBC.in 15 GB-NECs,the CT mutation was predominantamong the 6 types of SNVs.TP53 showed the highest mutation frequency(73%,11/15).Compared with neuroendocrine carcinomasof other organs,signifcantly mutated genes(SMGs)in GB-NECs were more similar to those in pulmonary large-cell euroendocrinecarcinomas(LCNECs),with drver roles for TP53 and RB1.Iin 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 ERB82 and ERBB3,were identified exclusively in GBC.Mutations in RB1 and NAB2 were significanty related to downregulation of the RB1 and NAB2 proteins,respectively,according to immunohistochemical(IHC)data(p values=0.0453 and0.0303).Clinically actionable genes indicated 23 mutated genes,including ALK,BRCA1,and BRCA2.Iin addition,potential somaticSNVs predicted by ISowN and SomVarlUS 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-RASpathways.In summary,we have systematically identified the mutation landscape of GB-NEC,and these findings may providemechanistic insights into the specifc pathogenesis of this deadly disease.
维普期刊数据库