Hypoxia increases the tempo of evolution in the peri-necrotic niche in glioblastoma

摘要: Glioblastoma is a deadly brain tumor characterized in part by the histological finding of pseudopallisading necrosis. The cause this necrosis can be multifactorial, but consequences are regions and hypoxia interspersed throughout tumors. This heterogeneity oxygen availability has significant influence on not only cellular population dynamics also treatment response. Further, been strongly correlated with emergence metastatic resistant phenotypes. As well as microenvironmental heterogeneity, glioblastoma one number cancers which have shown to composed proliferative hierarchy includes cells varying abilities recapitulate phenotype, most extreme recently labeled cancer stem cells, or initiating cells. interplay between explain glioblastomas somatic evolution neither clinical data nor biological models reality alone. Here we present computational agent-based model growing under heterogeneous domain. Our results show that tempo cell varies widely within tumor, particularly increased at peri-anoxic edge. We subsequently challenge provocative silico through analysis primary histologic samples taken from patients stained elucidate areas necrosis, identify p53. support hypothesis ridge increases turnover, leads an increase mutational load compared oxygenated environments. develop maps evolutionary histology find effectively warps velocity. Implications for both control discussed.