Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers.
Document Type
Article
Publication Date
2007
Keywords
Chromosomal-Instability, Chromosome-Aberrations, Conserved-Sequence, Genome, Humans, Leukemia-Lymphoma-Adult-T-Cell, Lymphoma-T-Cell, Mice, PTEN-Phosphohydrolase, Synteny
First Page
966
Last Page
971
JAX Source
Nature 2007 Jun; 447(7147):966-71.
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.
Recommended Citation
Maser RS,
Choudhury B,
Campbell PJ,
Feng B,
Wong KK,
Protopopov A,
O'Neil J,
Gutierrez A,
Ivanova E,
Perna I,
Lin E,
et a.
Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers. Nature 2007 Jun; 447(7147):966-71.