Pan-cancer analysis of intra-tumor heterogeneity

Each tumor is composed of diverse malignant, immune and stromal cells that interact with one another and collectively determine tumor biology and clinical phenotypes. We apply single cell RNA-seq (scRNA-seq) to diverse clinical tumor samples to comprehensively characterize the cellular diversity within tumors and explore the function of distinct tumor subpopulations. In this talk, I will describe our work on specific cancer types (e.g. glioma) and our pan-cancer integrative analysis of intra-tumor heterogeneity (ITH). We identify consistent patterns of heterogeneity across tumors, including expression meta-programs, consisting of dozens of genes that are coordinately upregulated in subpopulations of cells within many tumors. The meta-programs cover diverse cellular processes including both generic (e.g. cell cycle and stress) and lineage-specific patterns that influence metastasis, response to treatments and other tumor phenotypes.