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Prototypical oncogene family Myc defines unappreciated distinct lineage states of small cell lung cancer

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE156334 | GEO | 2020/12/31

REPOSITORIES: GEO

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Prototypical oncogene family Myc defines unappreciated distinct lineage states of small cell lung cancer [ATAC-seq]

Project description:Small cell lung cancer (SCLC) frequently harbors mutually exclusive genomic amplification of MYC family members. Therefore, it has been long suggested that they are functionally equivalent; however, more recently, their expression has been associated with specific neuroendocrine markers and distinct histopathology. Integrated transcriptomic and epigenomic analyses showed that c-Myc and L-Myc impart neuronal and non-neuroendocrine associated transcriptional programs, respectively, both associated with distinct SCLC lineage. Genetic replacement of c-Myc with L-Myc in c-Myc-SCLC induced a neuronal state but was insufficient to induce ASCL1 lineage. In contrast, c-Myc induced transition from ASCL1-SCLC to NeuroD1-SCLC characterized by distinct LCNEC-like histopathology. Collectively, we characterize an undescribed role of historically defined general oncogenes, c-Myc and L-Myc, for regulating lineage plasticity across molecular subtypes as well as histological subclasses.

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