LAUSR

Finally, this study suffers from underpowering, as it includes just 102 samples, less than half of which are the preinvasive AIS/MIA lesions of interest. Atypical alveolar hyperplasia, a presumed precursor of AIS, was not studied. Indeed, given the extensive genomic changes found in AIS/MIA, to truly understand early carcinogenesis, future studies must consider looking back to earlier preinvasive lesions, and even to the “normal” airways of smokers, as has been done in other tissues (14). Nevertheless, this study presents one of the largest cohorts published to date of preinvasive lung ADC, a rare disease state that is of great scientific interest given what it can teach us about cancer development. Several putative pathways for carcinogenesis are identified, providing candidates for experimental validation, and the implications for screening, diagnosis, and detection are significant. By stepping backward from invasive cancer into the earliest stages of carcinogenesis, this study represents an important step forward in our understanding of lung cancer evolution. n