title: Orthotopic xenografts of RCC retain histological, immunophenotypic and genetic features of tumours in patients.
abstract: Renal cell carcinoma (RCC) is an aggressive malignancy with limited responsiveness to existing treatments. 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).
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Chiara
authors.initials: C
authors.lastname: Grisanzio
authors.forename: Apryle
authors.initials: A
authors.lastname: Seeley
authors.forename: Michelle
authors.initials: M
authors.lastname: Chang
authors.forename: Michael
authors.initials: M
authors.lastname: Collins
authors.forename: Arianna
authors.initials: A
authors.lastname: Di Napoli
authors.forename: Su-Chun
authors.initials: SC
authors.lastname: Cheng
authors.forename: Andrew
authors.initials: A
authors.lastname: Percy
authors.forename: Rameen
authors.initials: R
authors.lastname: Beroukhim
authors.forename: Sabina
authors.initials: S
authors.lastname: Signoretti
mesh_terms: D000293:Adolescent; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007680:Kidney Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D014183:Transplantation, Heterologous