该研究团队使用了一个没有添加基因撞击或细胞类型偏倚的致癌物质诱导的LUSC模型，发现致癌物质暴露导致基底细胞之间的非中性竞争、异常克隆扩增和基底细胞沿气道的动员。最终，侵袭前病变由几个高度突变的克隆发展而来，这些克隆主宰了大部分支气管树。人类患者的多位点测序证实了在不同气道区域存在克隆相关的侵袭前病变。他们的工作确定了基底细胞克隆动力学的转变，以及相关的基底细胞命运的转变，作为肺场癌的驱动因素。
据悉，侵袭前肺鳞状病变是肺鳞状细胞癌（LUSC）的前兆。病变形成背后的细胞事件尚不清楚。
附：英文原文
Title: Aberrant basal cell clonal dynamics shape early lung carcinogenesis
Author: Sandra Gómez-López, Ahmed S. N. Alhendi, Moritz J. Przybilla, Ignacio Bordeu, Zoe E. Whiteman, Timothy Butler, Maral J. Rouhani, Lukas Kalinke, Imran Uddin, Kate E. J. Otter, Deepak P. Chandrasekharan, Marta Lebrusant-Fernandez, Abigail Y. L. Shurr, Pascal F. Durrenberger, David A. Moore, Mary Falzon, James L. Reading, Iigo Martincorena, Benjamin D. Simons, Peter J. Campbell, Sam M. Janes
Issue&Volume: 2025-06-12
Abstract: Preinvasive squamous lung lesions are precursors of lung squamous cell carcinoma (LUSC). The cellular events underlying lesion formation are unknown. Using a carcinogen-induced model of LUSC with no added genetic hits or cell type bias, we found that carcinogen exposure leads to non-neutral competition among basal cells, aberrant clonal expansions, and basal cell mobilization along the airways. Ultimately, preinvasive lesions developed from a few highly mutated clones that dominate most of the bronchial tree. Multisite sequencing in human patients confirmed the presence of clonally related preinvasive lesions across distinct airway regions. Our work identifies a transition in basal cell clonal dynamics, and an associated shift in basal cell fate, as drivers of field cancerization in the lung.
DOI: ads9145
Source: https://www.science.org/doi/10.1126/science.ads9145