Molecular Typing of Lung Adenocarcinoma on Cytological Samples in the Next-Generation Sequencing Era

Adenocarcinoma (AdC) is the most common subtype of lung cancer, the leading tumor worldwide for incidenceand mortality. In the majority of cases, a diagnosis is achieved only in advanced inoperable disease on cytological material obtained from pleural effusion, bronchoalveolarlavage, brushing, or fine-needle aspiration. Current recommendations provide for AdC to be tested for molecular alterations for which are already available targeted agents and many others are in clinical trials. However, conventional sequencing lacks of the necessary sensitivity to detect suchmolecular alterations in the scant cytological material and produces too many falsenegative results. Moreover, the number of therapeutically impacting markers that will need to be assessed is expected to rapidlyincrease. Thus, the application of highly sensitive and multigene probing methods, suchas those developed in the context of next-generation sequencing (NGS), has been recently introduced into clinical practice. NGS is able to detect and quantitate multiple gene alterations from limited amounts of DNA, thus improving the diagnostic and prognostic stratification of lung cancer patients, which is essential for personalized cancer therapy. This chapter yields the available dataabout NGS in this field.