Non-Genetic Intra-Tumor Heterogeneity Is a Major Predictor of Phenotypic Heterogeneity and Ongoing Evolutionary Dynamics in Lung Tumors.

ABSTRACT: Impacts of genetic and non-genetic intra-tumor heterogeneity (ITH) on tumor phenotypes and evolvability remain debated. We analyze ITH in lung squamous cell carcinoma at the levels of genome, transcriptome, and tumor-immune interactions and histopathological characteristics by multi-region bulk and single-cell sequencing. Genomic heterogeneity alone is a weak indicator of intra-tumor non-genetic heterogeneity at immune and transcriptomic levels that impact multiple cancer-related pathways, including those related to proliferation and inflammation, which in turn contribute to intra-tumor regional differences in histopathology and subtype classification. Tumor subclones have substantial differences in proliferation score, suggestive of non-neutral clonal dynamics. Proliferation and other can

SUBMITTER: Sharma A 

PROVIDER: S-EPMC6952742 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature