Stem Cell Hierarichies within Tumor Genetic Subclones

Abstract

Intratumoral heterogeneity has been appreciated at the genetic and transcriptional levels, yet it remains unclear how they relate to one another. My thesis project applies a novel qPCR technique to combine single-cell RNA-seq with same-cell cDNA genotyping at single-nucleotide resolution. Using whole-exome sequencing in a human oligodendroglioma tumor, we identified a mutation in CIC that is present in only a subset of cancer cells. A previous analysis of single-cell RNA-seq in this tumor showed a substantial minority of cancer cells that display a stemness phenotype distinct from differentiated lineage phenotypes previously known in low-grade glioma. Results of parallel qPCR genotyping demonstrate that both CIC-wild-type and CIC-mutant cells are found across the spectrum of stem-differentiated phenotypes. This suggests that the stemness phenotype exists independently of mutation status and that it is instead more likely epigenetically driven.