Dualistic classification of high grade serous ovarian carcinoma has its root in spatial heterogeneity

Overview of Tumor Heterogeneity in High-Grade Serous Ovarian Cancers

“…Multiple driving mutated events continuously stimulated original monoclonal origins and promoted tumor metastasis in the tree topology group. In contrast, in the star topology group, the tumor metastasis seems to be promoted by clustering of original polyclonal origins, supporting a parallel progression model of metastasis [56]. Most HGSOCs have Darwinian-based branching evolutionary patterns during tumorigenesis, with the divergence of subclones from a common ancestral clone [42].…”

“…In a recent study, Sun and colleagues proposed an evolutionary model for HGSOCs, dichotomizing HGSOCs into two topologies, one referring to a polyclonal origin and monophyletic/monoclonal spreading (star topology) with high genomic heterogeneity and the other monoclonal with polyphyletic or polyclonal spreading and low genetic heterogeneity (tree topology) [56]. Compared with star topology, in tree topology, a higher frequency of somatic abnormalities, higher ITH, and more driver events were detected in the spatiotemporal evolution of HGSOCs [56]. Multiple driving mutated events continuously stimulated original monoclonal origins and promoted tumor metastasis in the tree topology group.…”

“…The heterogeneity seems to be driven by stochastic and individually different genomic alterations from a constrained set of evolutionary moves that increase genomic instability and subclonal expansion [57]. Overall, the extensive spatial and temporal tumor heterogeneity found in HGSOC with multiple pathways leading to tumor relapse calls for multiple-site biopsy to guide clinical treatment [41,56].…”