Quantification of spatial subclonal interactions enhancing the invasive phenotype of pediatric glioma.

Diffuse midline gliomas (DMGs) are highly aggressive, incurable childhood brain tumors. They present a clinical challenge due to many factors, including heterogeneity and diffuse infiltration, complicating disease management. Recent studies have described the existence of subclonal populations that may co-operate to drive pro-tumorigenic processes such as cellular invasion. However, a precise quantification of subclonal interactions is lacking, a problem that extends to other cancers. In this study, we combine spatial computational modeling of cellular interactions during invasion with co-evolution experiments of clonally disassembled patient-derived DMG cells. We design a Bayesian inference framework to quantify spatial subclonal interactions between molecular and phenotypically distinct lineages with different patterns of invasion. We show how this approach could discriminate genuine interactions, where one clone enhanced the invasive phenotype of another, from those apparently only due to the complex dynamics of spatially restricted growth. This study provides a framework for the quantification of subclonal interactions in DMG. [Display omitted] • Explored the effects of interactions between cancer cells and their ability to spread • Developed a computational and experimental framework to study spatial interactions • Classified and quantified interactions present between two independent patient models • Identified the presence of a commensalism interaction between DIPG subclones Tari et al. explore interactions present between cancer cells and develop a methodology for their identification and quantification. Using a combination of computational modeling and experimental investigations, these interactions are demonstrated in pairs of single-cell-derived subclones isolated from independent patient tumors. [ABSTRACT FROM AUTHOR]