CDKN2A and small cell lung carcinoma: Although RB1 mutations emerge at a much lower rate in GEP-NEC compared to SCLC, the RB1 pathway appears to be suppressed by other mechanisms, such as copy number alterations affecting RB1, silencing of p16 via promoter methylation of cyclin-dependent kinase inhibitor 2A (CDKN2A), and amplifications of MYC or cyclin E1 (CCNE1) as an RB1 antagonist [10, 12, 45, 56, 58, 59].