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Publication : Cells of origin of lung cancers: lessons from mouse studies.

First Author  Ferone G Year  2020
Journal  Genes Dev Volume  34
Issue  15-16 Pages  1017-1032
PubMed ID  32747478 Mgi Jnum  J:301790
Mgi Id  MGI:6503991 Doi  10.1101/gad.338228.120
Citation  Ferone G, et al. (2020) Cells of origin of lung cancers: lessons from mouse studies. Genes Dev 34(15-16):1017-1032
abstractText  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.
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