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Clonal evolution in liver cancer at single-cell and single-variant resolution

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机构: [1]Shanghai Jiao Tong Univ, Shanghai Ctr Syst Biomed, Key Lab Syst Biomed, Minist Educ, Shanghai, Peoples R China [2]Shanghai Jiao Tong Univ, Biox Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Shanghai, Peoples R China [3]Fudan Univ, Huashan Hosp, Dept Gen Surg, Shanghai, Peoples R China [4]Fudan Univ, Canc Metastasis Inst, Shanghai, Peoples R China [5]Chinese Univ Hong Kong, Sch Biomed Sci, Key Lab Regenerat Med, Fac Med,Minist Educ, SAR, Hong Kong, Peoples R China [6]Univ Sydney, Sch Math & Stat, Sydney, NSW, Australia [7]Univ Sydney, Charles Perkins Ctr, Sydney, NSW, Australia [8]Univ Cambridge, Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Robinson Way, Cambridge CB2 0RE, England [9]Shanghai Jiao Tong Univ, Dept Pathol, Tongren Hosp, Sch Med, Shanghai, Peoples R China [10]Shanghai Jiao Tong Univ, Renji Hosp, Dept Urol, Sch Med, Shanghai, Peoples R China [11]Shanghai Jiao Tong Univ, Hongqiao Int Inst Med, Tongren Hosp, Sch Med, Shanghai, Peoples R China [12]Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Gen Surg, Sch Med, Shanghai, Peoples R China [13]Univ Sydney, Childrens Med Res Inst, Computat Syst Biol Grp, Westmead, NSW 2145, Australia
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关键词: Hepatocellular carcinoma Genetic heterogeneity Somatic mutation Clonal structure Tumor evolution

摘要:
Genetic heterogeneity of tumor is closely related to its clonal evolution, phenotypic diversity and treatment resistance, and such heterogeneity has only been characterized at single-cell sub-chromosomal scale in liver cancer. Here we reconstructed the single-variant resolution clonal evolution in human liver cancer based on single-cell mutational profiles. The results indicated that key genetic events occurred early during tumorigenesis, and an early metastasis followed by independent evolution was observed in primary liver tumor and intrahepatic metastatic portal vein tumor thrombus. By parallel single-cell RNA-Seq, the transcriptomic phenotype of HCC was found to be related with genetic heterogeneity. For the first time we reconstructed the single-cell and single-variant clonal evolution in human liver cancer, and dissection of both genetic and phenotypic heterogeneity will facilitate better understanding of their relationship.

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出版当年[2020]版:
大类 | 1 区 医学
小类 | 2 区 血液学 2 区 肿瘤学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 血液学 1 区 肿瘤学
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出版当年[2019]版:
Q1 HEMATOLOGY Q1 ONCOLOGY
最新[2023]版:
Q1 HEMATOLOGY Q1 ONCOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

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第一作者机构: [1]Shanghai Jiao Tong Univ, Shanghai Ctr Syst Biomed, Key Lab Syst Biomed, Minist Educ, Shanghai, Peoples R China
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通讯机构: [3]Fudan Univ, Huashan Hosp, Dept Gen Surg, Shanghai, Peoples R China [4]Fudan Univ, Canc Metastasis Inst, Shanghai, Peoples R China
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