Given the high prevalence of PIK3C2B mutations in the small NSCLC cohort screened by Liu et. al. and the connection to multiple steps of cancer progression, PIK3C2B and the reported kinase domain mutations C1181F and H1208R were closer examined in regard to promote aberrant PI3K signaling in NSCLC-SQCC. The gene discussed is PIK3C2B; the disease is cancer.