Integrative Identification by Hi‑C Revealed Distinct Advanced Structural Variations in Lung Adenocarcinoma Tissue

作     者：Tingting Song Menglin Yao Ying Yang Zhiqiang Liu Li Zhang Weimin Li 

作者机构：Department of Respiratory and Critical Care MedicineCenter of Precision MedicinePrecision Medicine Key Laboratory of Sichuan ProvinceFrontiers Science Center for Disease‑Related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina 

出 版 物：《Phenomics》 (表型组学（英文）)

年 卷 期：2023年第3卷第4期

页      面：390-407页

学科分类：0710[理学-生物学] 1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by National Guided Science and Technology Development Project of Sichuan Province(No:2020ZYD009) Clinical Research Incubation Project of West China Hospital of Sichuan University(No:2018HXFH012) Hospital-enterprise cooperation clinical research innovation project(Sichuan University West China Hospital-Shanghai Pharmaceutical)(No:2019HXCX04) Sichuan Science and Technology Program(No:2020ZYD007) Science and Technology Achievement Transformation Fund of Sichuan University West China Hospital(No:CGZH19013) we sincerely thanks to Biomarker Technologies Corporation(Beijing,China)for the analyses of bioinformation in this study. 

主　　题：High-throughput chromosome Lung cancer Advanced structural variations Chromosome 3 Tumor-related genes 

摘      要：Advanced three-dimensional structure variations of chromatin in large genome fragments,such as conversion of A/B compartment,topologically associated domains(TADs)and chromatin loops are related closely to occurrence of malignant tumors.However,the structural characteristics of lung cancer still remain uncovered.In this study,we used high-throughput chromosome(Hi-C)conformation capture technology to detect the advanced structural variations in chromatin of two nonsmoking lung adenocarcinoma(LUAD)tumor and paired normal tissues.The results indicate that significant chromatin variations are detected in tumor tissues compared with normal tissues.At compartment scale,the main conversion type of compartment is A→B in tumor tissues,which are concentrated mainly on chromosome 3(Chr3)(33.6%).A total of 216 tumor-specific TADs are identified in tumor tissues,which are distributed mainly in Chr1(19),Chr2(15)and Chr3(17).Forty-one distinct enhancer-promoter loops are observed in tumor tissue,which are associated closely to tumor-related pathways including mitogen-activated protein kinase(MAPK),Phosphatidylinositol-3-kinase-Protein kinase B(PI3K-AKT),Ras,Wnt and Ras1.The most important observation in this study is that we identify five important genes(SYT16,NCEH1,NXPE3,MB21D2,and DZIP1L),which are detected in both A→B compartment,TADs and chromatin loops in tumor samples,and four of these genes(NCEH1,NXPE3,MB21D2,and DZIP1L)locate on q arm of Chr3.Further gene expression and invasion experiment analysis show that NCEH1,MB21D2 and SYT16 are involved in the tumor development.Thus,we provide a comprehensive overview of advanced structures in LUAD for the first time and provide a basis for further research on the genetic variation of this tumor.