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The current molecular classification of small-cell lung cancer (SCLC) based on the expression of four lineage transcription factors still leaves its major subtype SCLC-A as a heterogeneous group, necessitating more precise characterization of lineage subclasses. To refine the current SCLC classification with epigenomic profiles and to identify features of the redefined SCLC subtypes. The study comprehensively describes additional epigenomic heterogeneity of the significant SCLC-A subtype. It defines the SCLC-Aα subtype by the core regulatory circuitry of NKX2-1 and SOX1 super-enhancers and their functional collaborations to maintain neuronal linage state.
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