Quantification of spatial subclonal interactions enhancing the invasive phenotype of pediatric glioma.
Abstract
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.
Collections
Subject
CP: Cancer
DIPG
cancer
computational
cooperation
heterogeneity
interactions
mathematical
pediatric
subclonal
Research team
Glioma Team
Evol Genomics & Modelling
Language
eng
Date accepted
2022-08-08
License start date
2022-08-30
Citation
Cell Reports, 2022, 40 (9), pp. 111283 -
Publisher
CELL PRESS