Preclinical xenograft models of human sarcoma show nonrandom loss of aberrations

Cancer. 2012 Jan 15;118(2):558-70. doi: 10.1002/cncr.26276. Epub 2011 Jun 28.


Background: Human tumors transplanted into immunodeficient mice (xenografts) are good preclinical models, and it is important to identify possible systematic changes during establishment and passaging in mice.

Methods: High-resolution microarray-based comparative genomic hybridization (array CGH) was used to investigate how well a series of sarcoma xenografts, including 9 patient/xenograft pairs and 8 early versus late xenograft passage pairs, represented the patient tumor from which they originated.

Results: In all analyses, the xenografts were more similar to their tumor of origin than other xenografts of the same type. Most changes in aberration patterns were toward a more normal genome complement, and the increased aberrations observed were mostly toward more loss. In general, the changes were scattered over the genome, but some changes were significant in osteosarcomas. These were rather focused and consistent with amplifications frequent in patient samples, involving the genes platelet-derived growth factor receptor A (PDGFRA), cysteine-rich hydrophobic domain 2 (CHIC2), FIP-like 1 (FIP1L1), ligand of numb-protein X1 (LNX1), RAS-like family 11 member B (RASL11B), and sec1 family domain containing 2 (SCFD2), probably a sign of continued tumor progression. Some changes that disappeared may have been involved in host-stroma interactions or chemotherapy resistance, possibly because of the absence of selection in the mouse.

Conclusions: Direct xenografts reflected well the genomic patterns of their tumors of origin. The few significant aberrations that were lost during passaging in immune-defective mice may have been caused by the lack of selection in the new host, whereas aberrations that were gained appeared to be the result of general tumor progression rather than model-specific artifacts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Child
  • Chromosome Aberrations
  • Comparative Genomic Hybridization
  • Disease Models, Animal*
  • Female
  • Humans
  • Male
  • Mice
  • Mice, SCID
  • Middle Aged
  • Neoplasm Transplantation
  • Sarcoma / genetics*
  • Transplantation, Heterologous*