Fig. 6: Syngeneic allograft models enable scalability for in vivo testing.
From: Somatic gene delivery faithfully recapitulates a molecular spectrum of high-risk sarcomas
a Schematics of syngeneic allograft modeling (SAM) procedure, systematically comparing four different allograft types. Created in BioRender. Banito, A. (2025) https://BioRender.com/abys0b6. b Tumor-free survival of SAMs compared to corresponding GEMMs. n ≥ 8 tumors per condition, including tumors with different genotypes. c tSNE analysis based on the top 10,000 differentially methylated CpG sites of SAMs, mouse-tumor-derived cell lines and corresponding GEMMs. d Median-ordered boxplots of Pearson correlation coefficients based on DNA methylation data from GEMMs and corresponding SAMs. n = 5 tumors per condition with 5 different genotypes. e Representative H&E histographs of GEMMs and corresponding SAMs after orthotopic engraftment of 2D-cultured mouse tumor lines. Scale bars equal 100 µm. f NTRKi in vitro sensitivity testing. Data points correspond to asymmetric drug sensitivity scores (DSS, as explained in the methods). DDS = 0 indicates resistance, and values > 10 indicate sensitivity. n ≥ 2 cell lines grouped by entity, in two independent experiments (triangles and squares). For the IMT condition, only one cell line was available. IMT refers to a human tumor cell line derived from an Inflammatory myofibroblastic tumor driven by ETV6::NTRK3 used to clone the mouse transposon vectors for electroporation. Three eRMS (KRASG12V/sgTrp53) tumor lines were used as fusion negative controls for comparison. Boxplots in b, d, and f display individual values, median, interquartile range (IQR). Whiskers extend to the most extreme data points within 1.5 times the IQR from the lower and upper quartiles. P values refer to unpaired two-sided t-tests, corrected for multiple testing using the Bonferroni-Holm method. g In vivo treatment of FD-IFS tumor line re-engrafted orthotopically into wildtype C57BL6/J host mice. Treatment started when mice developed palpable tumors (days 8–10 post engraftment) by oral gavage of NTRK inhibitors or vehicle twice a day. Mean, standard deviation and individual values are depicted. n = 8 mice per group. Source data are provided as a Source data file.