Genomic Heterogeneity and Clonal Evolution in Gastroesophageal Junction Cancer Revealed by Single Cell DNA Sequencing.
Genomic Heterogeneity and Clonal Evolution in Gastroesophageal Junction Cancer Revealed by Single Cell DNA Sequencing.
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单细胞 DNA 测序揭示胃食管结合部癌的基因组异质性和克隆进化
DOI：
10.3389/fonc.2021.672020
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发表时间：
2021
影响因子：
4.7
通讯作者：
Xu B
中科院分区：
文献类型：
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作者：
Duan Q;Tang C;Ma Z;Chen C;Shang X;Yue J;Jiang H;Gao Y;Xu B
胃食管交界处癌（GEJ）是解剖上发生在胃和食管交界处的肿瘤。GEJ癌经常转移到淋巴结，但异质性和克隆进化过程尚不清楚。这项研究是首次使用单细胞DNA测序来确定与淋巴结转移相关的基因组变异和克隆进化。采用多重退火和环状扩增循环（MALBAC）和大量外显子组测序分别检测单细胞拷贝数变异（CNVs）和单核苷酸变异（SNVs）。4例GEJ癌患者入组，其中2例（Pt.3, Pt.4）有转移性淋巴结。我们发现最常见的突变发生在TTN基因上，据报道，该基因与癌症的肿瘤突变负担有关。SNVs和CNVs存在显著的患者内部异质性。我们在每个肿瘤中确定了SNV亚克隆结构。为了研究CNVs的异质性，对单细胞进行了测序。原发肿瘤中的亚克隆数量大于淋巴结中的亚克隆数量，表明原发部位的异质性更高。我们观察到两种多站淋巴结转移模式：一种是跳跃转移，另一种是跟随淋巴引流。总之，我们的单细胞基因组分析揭示了GEJ癌的异质性和克隆进化。
Gastroesophageal junction (GEJ) cancer is a tumor that occurs at the junction of stomach and esophagus anatomically. GEJ cancer frequently metastasizes to lymph nodes, however the heterogeneity and clonal evolution process are unclear. This study is the first of this kind to use single cell DNA sequencing to determine genomic variations and clonal evolution related to lymph node metastasis. Multiple Annealing and Looping Based Amplification Cycles (MALBAC) and bulk exome sequencing were performed to detect single cell copy number variations (CNVs) and single nucleotide variations (SNVs) respectively. Four GEJ cancer patients were enrolled with two (Pt.3, Pt.4) having metastatic lymph nodes. The most common mutation we found happened in the TTN gene, which was reported to be related with the tumor mutation burden in cancers. Significant intra-patient heterogeneity in SNVs and CNVs were found. We identified the SNV subclonal architecture in each tumor. To study the heterogeneity of CNVs, the single cells were sequenced. The number of subclones in the primary tumor was larger than that in lymph nodes, indicating the heterogeneity of primary site was higher. We observed two patterns of multi-station lymph node metastasis: one was skip metastasis and the other was to follow the lymphatic drainage. Taken together, our single cell genomic analysis has revealed the heterogeneity and clonal evolution in GEJ cancer.
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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：
64.8
作者：
Cancer Genome Atlas Research Network;Analysis Working Group: Asan University;BC Cancer Agency;Brigham and Women’s Hospital;Broad Institute;Brown University;Case Western Reserve University;Dana-Farber Cancer Institute;Duke University;Greater Poland Cancer Centre;Harvard Medical School;Institute for Systems Biology;KU Leuven;Mayo Clinic;Memorial Sloan Kettering Cancer Center;National Cancer Institute;Nationwide Children’s Hospital;Stanford University;University of Alabama;University of Michigan;University of North Carolina;University of Pittsburgh;University of Rochester;University of Southern California;University of Texas MD Anderson Cancer Center;University of Washington;Van Andel Research Institute;Vanderbilt University;Washington University;Genome Sequencing Center: Broad Institute;Washington University in St. Louis;Genome Characterization Centers: BC Cancer Agency;Broad Institute;Harvard Medical School;Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University;University of North Carolina;University of Southern California Epigenome Center;University of Texas MD Anderson Cancer Center;Van Andel Research Institute;Genome Data Analysis Centers: Broad Institute;Brown University:;Harvard Medical School;Institute for Systems Biology;Memorial Sloan Kettering Cancer Center;University of California Santa Cruz;University of Texas MD Anderson Cancer Center;Biospecimen Core Resource: International Genomics Consortium;Research Institute at Nationwide Children’s Hospital;Tissue Source Sites: Analytic Biologic Services;Asan Medical Center;Asterand Bioscience;Barretos Cancer Hospital;BioreclamationIVT;Botkin Municipal Clinic;Chonnam National University Medical School;Christiana Care Health System;Cureline;Duke University;Emory University;Erasmus University;Indiana University School of Medicine;Institute of Oncology of Moldova;International Genomics Consortium;Invidumed;Israelitisches Krankenhaus Hamburg;Keimyung University School of Medicine;Memorial Sloan Kettering Cancer Center;National Cancer Center Goyang;Ontario Tumour Bank;Peter MacCallum Cancer Centre;Pusan National University Medical School;Ribeirão Preto Medical School;St. Joseph’s Hospital &Medical Center;St. Petersburg Academic University;Tayside Tissue Bank;University of Dundee;University of Kansas Medical Center;University of Michigan;University of North Carolina at Chapel Hill;University of Pittsburgh School of Medicine;University of Texas MD Anderson Cancer Center;Disease Working Group: Duke University;Memorial Sloan Kettering Cancer Center;National Cancer Institute;University of Texas MD Anderson Cancer Center;Yonsei University College of Medicine;Data Coordination Center: CSRA Inc.;Project Team: National Institutes of Health
通讯作者：
Project Team: National Institutes of Health
DOI：
10.1093/bioinformatics/btr670
发表时间：
2012-02-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Boeva V;Popova T;Bleakley K;Chiche P;Cappo J;Schleiermacher G;Janoueix-Lerosey I;Delattre O;Barillot E
通讯作者：
Barillot E
影响因子：
64.8
作者：
Navin N;Kendall J;Troge J;Andrews P;Rodgers L;McIndoo J;Cook K;Stepansky A;Levy D;Esposito D;Muthuswamy L;Krasnitz A;McCombie WR;Hicks J;Wigler M
通讯作者：
Wigler M
使用下一代 DNA 测序数据进行变异发现和基因分型的框架。
影响因子：
30.8
作者：
通讯作者：
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