Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers Academic Article uri icon

Overview

MeSH Major

  • Chromosomal Instability
  • Chromosome Aberrations
  • Conserved Sequence
  • Leukemia-Lymphoma, Adult T-Cell
  • Lymphoma, T-Cell

abstract

  • Highly rearranged and mutated cancer genomes present major challenges in the identification of pathogenetic events driving the neoplastic transformation process. Here we engineered lymphoma-prone mice with chromosomal instability to assess the usefulness of mouse models in cancer gene discovery and the extent of cross-species overlap in cancer-associated copy number aberrations. Along with targeted re-sequencing, our comparative oncogenomic studies identified FBXW7 and PTEN to be commonly deleted both in murine lymphomas and in human T-cell acute lymphoblastic leukaemia/lymphoma (T-ALL). The murine cancers acquire widespread recurrent amplifications and deletions targeting loci syntenic to those not only in human T-ALL but also in diverse human haematopoietic, mesenchymal and epithelial tumours. These results indicate that murine and human tumours experience common biological processes driven by orthologous genetic events in their malignant evolution. The highly concordant nature of genomic events encourages the use of genomically unstable murine cancer models in the discovery of biological driver events in the human oncogenome.

authors

publication date

  • June 21, 2007

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2714968

Digital Object Identifier (DOI)

  • 10.1038/nature05886

PubMed ID

  • 17515920

Additional Document Info

start page

  • 966

end page

  • 71

volume

  • 447

number

  • 7147