Fig. 1

Generation of a genomically heterogeneous PDX model of TNBC. a Establishment of the PDX model PIM001-P. FNA, fine-needle aspirate biopsy. MFP, mammary fat pad. b Pictomicrographs of H&E-stained sections of the patient’s tumor and PDX tumors are shown. Images are 10×, and insets are 40× magnification. Scale bars represent 100 μm. c The mutant allele frequencies (MAFs) of mutations detected by WES and validated by targeted sequencing were compared with each other and with MAFs of the patient’s tumor. Mutations in COSMIC cancer genes are shown in red. Pearson Correlation Coefficients (PCC) are shown in the bottom right corner of each plot. d Circos plots were generated to visualize genomic structural rearrangements in patient and PDX tumors. Chromosomes are demarcated by distinct colors. e PIM001-P tumor cells were engineered to express click beetle red luciferase (CBRLuc) and mCherry. Following lentiviral transduction, mCherry-positive tumor cells were sorted by FACS and engrafted into the MFP of a NOD/SCID mouse. Tumors were isolated and re-passaged into recipient mice and mCherry positivity was confirmed at each passage by flow cytometry. BLI identified lung, liver, brain, and bone metastases in engrafted mice. In most cases, MFP tumors regrew in the primary site following surgical resection. f Percentage of engrafted mice with metastases in indicated organs (n = 20)