Molecular characterization of patient-derived human pancreatic tumor xenograft models for preclinical and translational development of cancer therapeutics

摘要: Preclinical evaluation of novel cancer agents requires models that accurately reflect the biology and molecular characteristics human tumors. Molecular profiles eight pancreatic ductal adenocarcinoma patient tumors were compared to corresponding passages xenografts obtained by grafting tumor fragments into immunocompromised mice. characterization was performed copy number analysis, gene expression microRNA microarrays, mutation short tandem repeat (STR) profiling, immunohistochemistry. Xenografts found be highly representative their respective tumors, with a high degree genetic stability observed STR profiling analysis. Copy variation (CNV) early late xenograft similar, recurrent losses on chromosomes 1p, 3p, 4q, 6, 8p, 9, 10, 11q, 12p, 15q, 17, 18, 20p, 21 gains 1q, 5p, 8q, 12q, 13q, 19q, 20q. Pearson correlations above 0.88 for all models. Gene patterns between passage stable each individual model. Changes in largely corresponded stromal compartment genes inflammatory processes. While some differences exist primary xenografts, remain after extensive passaging. Evidence several rounds passaging lends confidence clinical relevance allows expansion generate requisite animals required cohorts used drug screening development studies.