Modeling the effect of spatial structure on solid tumor evolution and ctDNA composition.

ABSTRACT: Circulating tumor DNA (ctDNA) monitoring, while sufficiently advanced to reflect tumor evolution in real time and inform on cancer diagnosis, treatment, and prognosis, mainly relies on DNA that originates from cell death via apoptosis or necrosis. In solid tumors, chemotherapy and immune infiltration can induce spatially variable rates of cell death, with the potential to bias and distort the clonal composition of ctDNA. Using a stochastic evolutionary model of boundary-driven growth, we study how elevated cell death on the edge of a tumor can simultaneously impact driver mutation accumulation and the representation of tumor clones and mutation detectability in ctDNA. We describe conditions in which invasive clones end up over-represented in ctDNA, clonal diversity can appear elevated in t

SUBMITTER: Rachman T 

PROVIDER: S-EPMC10659436 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature