Extrachromosomal DNA Amplification Contributes to Small Cell Lung Cancer Heterogeneity and is Associated with Worse Outcomes. Homo sapiens

Small-cell lung cancer (SCLC) is a very aggressive neuroendocrine lung cancer often associated with oncogenic MYC amplifications which is known to drive SCLC heterogeneity marked by neuroendocrine (NE) and non-neuroendocrine (non-NE) cell states. The genetic mechanisms of MYC amplification and phenotypic plasticity between cell states is not known. Using data from cell-lines and few patient derived samples along with integrated whole-genome sequencing, long-range optical mapping, single-cell DNA sequencing, and fluorescence in situ hybridization we have attempted to successfully find extrachromosomal DNA (ecDNA) as the primary source of MYC amplifications and driver fusions in SCLC.