Orthotopic xenografts of RCC retain histological, immunophenotypic and genetic features of tumours in patients.

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In vivo models of human cancer, including RCC, are critical for developing more effective therapies. Unfortunately, current RCC models do not accurately represent relevant properties of the human disease. The goal of this study was to develop clinically relevant animal models of RCC for preclinical investigations. We transplanted intact human tumour tissue fragments orthotopically in immunodeficient mice. The xenografts were validated by comparing the morphological, phenotypic and genetic characteristics of the kidney tumour tissues before and after implantation. Twenty kidney tumours were transplanted into mice. Successful tumour growth was detected in 19 cases (95%). The histopathological and immunophenotypic features of the xenografts and those of the original tumours largely overlapped in all cases. Evaluation of genetic alterations in a subset of 10 cases demonstrated that the grafts largely retained the genetic features of the pre-implantation RCC tissues. Indeed, primary tumours and corresponding grafts displayed identical VHL mutations. Moreover, an identical pattern of DNA copy amplification or loss was observed in 6/10 cases (60%). In summary, orthotopic engrafting of RCC tissue fragments can be successfully used to generate animal models that closely resemble RCC in patients. These models will be invaluable for in vivo preclinical drug testing and for deeper understanding of kidney carcinogenesis. The raw data of the SNP array analysis has been submitted to the GEO database (Accession No. GSE29062).", "claims": [{"id": "claim-target-result", "statement": "Orthotopic engrafting of RCC tissue fragments can successfully generate animal models that closely resemble RCC in patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:21710693", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "In summary, orthotopic engrafting of RCC tissue fragments can be successfully used to generate animal models that closely resemble RCC in patients."}, {"asset": "source:pmid:21710693", "locator": "sections[8] \"Genetic analyses\" paragraph 3", "quote": "Von Hippel-Lindau gene (VHL) mutational analysis was performed by direct sequencing. as previously described (26)."}, {"asset": "source:pmid:21710693", "locator": "sections[8] \"Genetic analyses\" paragraph 3", "quote": "For DNA copy number analysis, the Sty I (250K) SNP array of the 500K Human Mapping Array (Affymetrix) was used."}, {"asset": "source:pmid:21710693", "locator": "sections[12] \"Orthotopic RCC grafts retain the genetic characteristics of the original human tumors\" paragraph 2", "quote": "There was no significant association between VHL mutational status and the average graft volume (exact Wilcoxon-Mann-Whitney test, p = 1)"}, {"asset": "source:pmid:21710693", "locator": "sections[12] \"Orthotopic RCC grafts retain the genetic characteristics of the original human tumors\" paragraph 5", "quote": "Of note, we found a positive association between the number of non-random genetic changes in the grafts and the average graft volume (exact Spearman's correlation test, p = 0.033)."}, {"asset": "source:pmid:21710693", "locator": "sections[13] \"Orthotopic RCC grafts develop metastases\" paragraph 3", "quote": "There was no significant association between the grade of the human RCC and the aggressiveness (i.e. local invasion and/or metastases) of the corresponding xenografts (Fisher's exact test, p = 0.38)."}, {"asset": "source:pmid:21710693", "locator": "sections[17] \"fn-group\" paragraph 1", "quote": "The raw data of the SNP array analysis is in the process of being deposited in the GEO database."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Orthotopic engrafting of RCC tissue fragments can successfully generate animal models that closely resemble RCC in patients.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:21710693"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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