American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Mar 2020
Genomic Underpinnings of Tumor Behavior in in situ and Early Lung Adenocarcinoma.
Rationale: We have a limited understanding of the molecular underpinnings of early adenocarcinoma (ADC) progression. We hypothesized that the behavior of early ADC can be predicted based on genomic determinants. Objectives: To identify genomic alterations associated with resected indolent and aggressive early lung ADCs. ⋯ Mutations of KRAS, TP53, and NF1 were found to increase in frequency from AIS and MIA to ADC. A cancer progression model revealed selective early and late drivers. Conclusions: Our results reveal several genetic driver events, clonality, and mutational signatures associated with poor outcome in early lung ADC, with potential future implications for the detection and management of ADC.