Figure 6 from Extrachromosomal DNA–Driven Oncogene Spatial Heterogeneity and Evolution in Glioblastoma

Le résumé fourni par la source

Simulating multi-ecDNA dynamics in vivo.A, DNA FISH and nascent RNAscope images from the tumor of patient A5, showing the coexistence of both EGFR-ecDNA and PDGFRA-ecDNA. B, Circular structures of three distinct oncogenic ecDNAs detected in the tumor of patient A5. C, GBMs in the GB-UK and PCAWG cohorts containing more than one oncogenic species and their respective copy numbers. D, In a multiple-ecDNA application of SPECIES, the clone-initiating cell begins with k1 and k2 copies of ecDNA 1 and ecDNA 2, respectively. E, Representation of the impacts of ecDNA cosegregation and coselection on the number of inherited ecDNA copies during cell division. Cosegregation drives correlated inheritance of both ecDNA types, whereas coselection favors tumor cells carrying at least one copy of each type. F, Application of SPECIES to simulate two separate ecDNA species. Simulated tumors were initialized with a single cell, carrying k1 and k2 copies of each ecDNA species. Representative model images show examples of low and high cosegregation and coselection. G and H, Parameter inference summary for the tumor of patient A5, for which we measured both the EGFR-ecDNA and PDGFRA-ecDNA copy-number distributions using DNA FISH, using multiple-ecDNA SPECIES. Parameters sp and sm represent selection coefficients for tumor cells with 1 (pure) or 2 (mixed) ecDNA species, respectively. I, Comparison of inferred k and k1 values for all patient tumors confirmed by WGS to harbor two or more ecDNA species. J, The presence of ecDNA amplifications may be used to aid stratification, given that oncogenes on ecDNA have an inherent resistance mechanism through the ability of ecDNA to dynamically adjust copy number in response to targeted agents. Earlier monitoring and intervention are recommended for those patient tumors with ecDNA that will receive targeted therapies.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.