In EGFR-mutated NSCLC, baseline inactivation of RB1 and TP53 are associated with a 43-fold increase in the risk of small cell transformation, although the mechanisms underlying transformation are yet to be elucidated.84,85 Transformation from EGFR-mutated and ALK+ lung adenocarcinoma to squamous cell carcinoma has also been described.86,87 Histologic transformation, albeit infrequent, underscores the importance of obtaining a tissue biopsy at disease progression to understand disease biology and determine treatment options. This evidence concerns the gene EGFR and lung adenocarcinoma.