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Abstract：
Biliary tract cancers (BTCs) are aggressive epithelial malignancies that can arise at any point of the biliary tree. Albeit rare, their incidence and mortality rates have been rising steadily over the past 40 years, highlighting the need to improve current diagnostic and therapeutic strategies. BTCs show high inter- and intra-tumour heterogeneity both at the morphological and molecular level. Such complex heterogeneity poses a substantial obstacle to effective interventions. It is widely accepted that the observed heterogeneity may be the result of a complex interplay of different elements, including risk factors, distinct molecular alterations and multiple potential cells of origin. The use of genetic lineage tracing systems in experimental models has identified cholangiocytes, hepatocytes and/or progenitor-like cells as the cells of origin of BTCs. Genomic evidence in support of the distinct cell of origin hypotheses is growing. In this review, we focus on recent advances in the histopathological subtyping of BTCs, discuss current genomic evidence and outline lineage tracing studies that have contributed to the current knowledge surrounding the cell of origin of these tumours.
摘要：
胆道癌（BTC）是侵袭性上皮恶性肿瘤，可在胆道树的任何部位出现。尽管很罕见，在过去的40年里，它们的发病率和死亡率一直在稳步上升，强调需要改进当前的诊断和治疗策略。BTC在形态和分子水平上都显示出高的肿瘤间和肿瘤内异质性。这种复杂的异质性对有效的干预措施构成了实质性障碍。人们普遍认为，观察到的异质性可能是不同元素复杂相互作用的结果，包括风险因素，不同的分子改变和多个潜在的起源细胞。在实验模型中使用遗传谱系追踪系统已经确定了胆管细胞，肝细胞和/或祖细胞样细胞作为BTC的起源细胞。支持不同起源细胞假说的基因组证据正在增加。在这次审查中,我们关注BTC组织病理学亚型的最新进展，讨论当前的基因组证据，并概述谱系追踪研究，这些研究有助于围绕这些肿瘤的起源细胞的当前知识。
