As one of the most common forms of cancer, lung cancers present as a collection of different histological subtypes. These subtypes are characterized by distinct sets of driver mutations and phenotypic appearance, and they often show varying degrees of heterogenicity, aggressiveness, and response/resistance to therapy. Intriguingly, lung cancers are also capable of showing features of multiple subtypes or converting from one subtype to another. The intertumoral and intratumoral heterogeneity of lung cancers as well as incidences of subtype transdifferentiation raise the question of to what extent the tumor characteristics are dictated by the cell of origin rather than the acquired driver lesions. We provide here an overview of the studies in experimental mouse models that try to address this question. These studies convincingly show that both the cell of origin and the genetic driver lesions play a critical role in shaping the phenotypes of lung tumors. However, they also illustrate that there is far from a direct one-to-one relationship between the cell of origin and the cancer subtype, as most epithelial cells can be reprogrammed toward diverse lung cancer fates when exposed to the appropriate set of driver mutations.

中文翻译：

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肺癌起源细胞：小鼠研究的教训。


作为最常见的癌症形式之一，肺癌表现为不同组织学亚型的集合。这些亚型的特点是具有不同的驱动突变组和表型外观，并且它们通常表现出不同程度的异质性、攻击性和对治疗的反应/耐药性。有趣的是，肺癌还能够表现出多种亚型的特征或从一种亚型转变为另一种亚型。肺癌的瘤间和瘤内异质性以及亚型转分化的发生率提出了一个问题：肿瘤特征在多大程度上是由起源细胞而不是获得性驱动病变决定的。我们在这里概述了试图解决这个问题的实验小鼠模型的研究。这些研究令人信服地表明，起源细胞和遗传驱动病变在塑造肺部肿瘤的表型中发挥着关键作用。然而，他们还表明，起源细胞和癌症亚型之间远非直接的一对一关系，因为当暴露于适当的驱动突变组时，大多数上皮细胞可以重新编程以实现不同的肺癌命运。