We applied a multi-region sampling and single cell sequencing approach to assess mutational diversity and gain insight into tumor evolutionary dynamics in two primary GBMs, one harboring an EGFR amplification and the other was wild-type at EGFR locus according to the clinical information.
We applied a multi-region sampling and single cell sequencing approach to assess mutational diversity and gain insight into tumor evolutionary dynamics in two primary GBMs, one harboring an EGFR amplification and the other was wild-type at EGFR locus according to the clinical information. We first determined the genetic heterogeneity in distinct lesion regions within individual tumors at both genomic alteration and gene-expression signature. We then profiled cell specific alterations through multi-regional single cell sequencing (MRSCS), which further indicated mutational diversity during tumor development and how cell cohorts with concordant alterations were generated. Our analysis subsequently characterized the development process in both GBMs sequenced by pinpointing alteration events in distinct cell populations, and we demonstrated that different GBMs have diverse evolutionary dynamics. This study hence provides essential implications for dissecting cancer progression and introduces approach for precision medicine in clinical application.