Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers.

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: Richard S Maser, Bhudipa Choudhury, Peter J Campbell, Bin Feng, Kwok-Kin Wong, Alexei Protopopov, Jennifer O'Neil, Alejandro Gutierrez, Elena Ivanova, Ilana Perna, Eric Lin, Vidya Mani, Shan Jiang, Kate McNamara, Sara Zaghlul, Sarah Edkins, Claire Stevens, Cameron Brennan, Eric S Martin, Ruprecht Wiedemeyer, Omar Kabbarah, Cristina Nogueira, Gavin Histen, Jon Aster, Marc Mansour, Veronique Duke, Letizia Foroni, Adele K Fielding, Anthony H Goldstone, Jacob M Rowe, Yaoqi A Wang, A Thomas Look, Michael R Stratton, Lynda Chin, P Andrew Futreal, Ronald A DePinho
• Journal: Nature (Nature) Vol. 447 Issue 7147 Pg. 966-71 (Jun 21 2007) ISSN: 1476-4687 [Electronic] England
• PMID: 17515920 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• PTEN Phosphohydrolase

Topics

• Animals
• Chromosomal Instability (genetics)
• Chromosome Aberrations
• Conserved Sequence (genetics)
• Genome (genetics)
• Humans
• Leukemia-Lymphoma, Adult T-Cell (genetics)
• Lymphoma, T-Cell (genetics)
• Mice
• PTEN Phosphohydrolase (deficiency, genetics)
• Synteny (genetics)