Stochastic modelling of single-cell gene expression adaptation reveals non-genomic contribution to evolution of tumor subclones.

ABSTRACT: Cancer progression is an evolutionary process driven by the selection of cells adapted to gain growth advantage. We present the first formal study on the adaptation of gene expression in subclonal evolution. We model evolutionary changes in gene expression as stochastic Ornstein-Uhlenbeck processes, jointly leveraging the evolutionary history of subclones and single-cell expression data. Applying our model to sublines derived from single cells of a mouse melanoma revealed that sublines with distinct phenotypes are underlined by different patterns of gene expression adaptation, indicating non-genetic mechanisms of cancer evolution. Interestingly, sublines previously observed to be resistant to anti-CTLA-4 treatment showed adaptive expression of genes related to invasion and non-canonical Wn

SUBMITTER: Hirsch MG 

PROVIDER: S-EPMC11071284 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature