Fig. 2: Histological and genomic comparison of patient tumors and paired patient-derived models. | Nature Communications

Fig. 2: Histological and genomic comparison of patient tumors and paired patient-derived models.

From: Modeling biological and genetic diversity in upper tract urothelial carcinoma with patient derived xenografts

Fig. 2

a UTUC tumors and corresponding PDX models demonstrated similar histological features as assessed by H&E staining. Scale bar corresponds to 200 µm. H&E slides of a section of each patient tumor (UCC03, n = 3; UCC14, n = 1; UCC17, n = 1; UCC15, n = 1), matching PDX (UCC03, n = 3; UCC14, n = 2; UCC17, n = 2; UCC15, n = 1) and matching cell line/cell line-derived xenograft (UCC03, n = 1; UCC14, n = 1; UCC17, n = 1) were reviewed by a board-certified pathologist (H.A-A.) and representative pictures are shown. b Concordance of selected cancer-associated genes for the 17 tumors and paired PDX models that successfully engrafted in mice [a: primary tumor, b: lymph node metastasis, c: distal metastasis, d: PDX at early passage (P1-P3), e: PDX at late passage (P4-P6), f: cell line/cell line-derived xenograft]. The UCC03 and UCC11 PDX models were established from abdominal wall and liver resections, respectively, whereas UCC32 was from a lymph node. The UCC11 PDX was generated from the frozen cell pellet of a patient specimen. All others were established from primary tumors. c Concordance of somatic oncogenic mutations of the patient tumor and corresponding PDX models and tumor mutational burden (TMB) of the patient tumors. Four PDX models were derived from MSI-H tumors (right panel, green and blue). d Phylogenetic analysis of whole-exome sequencing data for two patients (UCC30 and UCC03) revealed evidence of linear and branched tumor evolution [P: primary, M: metastasis, PDX: X1 (early passage) and X2 (late passage) which represent replicates of different passage numbers, CL: PDC]. The number of mutations is shown between branch points. e AID/APOBEC mutational signatures (Signatures 2 and 13) were predominant in UCC30 and UCC03 patient tumors while AID/APOBEC(2) was lost in UCC30 PDX. The mutation signatures with FDR < 0.05 are shown. Data are presented as mean values ± SD. Source data for b–e are provided as a Source Data file.

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