E-GEOD-34412 - A Renewable Tissue Resource of Phenotypically Stable, Biologically and Ethnically Diverse, Patient-derived Human Breast Cancer Xenografts

Status
Released on 25 June 2013, last updated on 4 May 2014
Organism
Homo sapiens
Samples (120)
Array (1)
Protocols (5)
Description
Translational breast cancer research is hampered by difficulties in obtaining and studying primary human breast tissue, and by the lack of in vivo preclinical models that reflect patient tumor biology accurately. In an effort to overcome these limitations, we propagated a cohort of human breast tumors grown in the mammary fat pad of SCID/Beige and NOD/SCID/IL2?-receptor null (NSG) two relatively new immunocompromised mouse models, under a series of transplant conditions. Both models yielded stably transplantable xenografts relatively high rates compared with previously available immunocompromised mice. Xenograft lines were established directly from breast cancer patient samples, without intervening culture in vitro, using the epithelium-free mammary fat pad as the transplantation site. Of the conditions tested, xenograft take rate was highest in the presence of a low-dose estradiol pellet. Overall, 35 stably transplantable xenograft lines representing 27 patients were established, using pre-treatment, mid-treatment, and/or post-treatment samples. Most patients yielding xenografts were “triple-negative” (ER-PR-HER2-) (n=21). However, we were able to establish lines from three ER-PR-HER2+ patients, one ER+PR-HER2-, one ER+PR+HER2- and one “triple-positive” (ER+PR+HER2+) patient. Serially passaged xenografts show biological consistency with the tumor of origin at the histopathology level, and remarkable stability across multiple transplant generations at the genomic, transcriptomic, and proteomic levels. Of the 27 patients represented, xenografts derived from 13 patients showed metastasis to the mouse lung. These models thus serve as a renewable, quality-controlled tissue resource, and should prove useful for preclinical evaluation of experimental therapeutics. reference x sample
Experiment type
transcription profiling by array 
Contacts
Charles Perou <cperou@med.unc.edu>, Aleix Prat, Charles M Perou, Xiaomei Zhang
Citation
A Renewable Tissue Resource of Phenotypically Stable, Biologically and Ethnically Diverse, Patient-derived Human Breast Cancer Xenografts. Zhang X, Claerhout S, Prat A, Dobrolecki L, Petrovic I, Lai Q, Landis M, Wiechmann L, Schiff R, Giuliano M, Wong H, Fuqua S, Contreras A, Gutierrez C, Huang J, Mao S, Pavlick A, Froehlich AM, Wu MF, Tsimelzon A, Hilsenbeck SG, Chen E, Zuloaga P, Shaw C, Rimawi MF, Perou CM, Mills GB, Chang JC, Lewis MT. , Europe PMC 23737486
MIAME
PlatformsProtocolsFactorsProcessedRaw
Files
Links