Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai, China.
J Hematol Oncol. 2021 Feb 2;14(1):22. doi: 10.1186/s13045-021-01036-y.
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.
肿瘤的遗传异质性与其克隆进化、表型多样性和治疗耐药性密切相关，这种异质性仅在肝癌的单细胞亚染色体尺度上得到了描述。在这里，我们基于单细胞突变谱重建了人类肝癌的单变体分辨率克隆进化。结果表明，关键的遗传事件发生在肿瘤发生的早期，在原发性肝癌和肝内转移性门静脉癌栓中观察到早期转移后独立进化。通过平行的单细胞 RNA-Seq，发现 HCC 的转录组表型与遗传异质性有关。我们首次重建了人类肝癌的单细胞和单变体克隆进化，对遗传和表型异质性的剖析将有助于更好地理解它们之间的关系。
