ES27.04 Phenotypic Heterogeneity

Tumor evolution from a single cell into malignant tissue comprised of diverse populations remains poorly understood. We profiled transcriptomes genetically engineered mouse lung tumors at eight stages spanning tumor progression atypical adenomatous hyperplasia to adenocarcinoma. The diversity transcriptional states spanned by cells increased over time and was reproducible across mice, but not explained genomic copy number variation. Cancer progressively adopted alternate lineage identities, computationally predicted be mediated through common transitional, high-plasticity state (HPCS). HPCS prospectively isolated had robust potential for phenotypic switching formation, were more chemoresistant in mice. Putative human patient-derived cancer xenografts displayed high plasticity sphere-forming capacity. program associated with poor survival adenocarcinoma cancers. I will discuss transitions that connect the targeting HPCS. Heterogeneity, evolution,