E-GEOD-7600 - Transcription profiling of mouse Atm-/-,mTerc-/-,p53-/- triple knock out lymphoma vs. normal mouse DNA (GPL2884)
Submitted on 24 April 2007, released on 15 June 2008, last updated on 2 May 2014
Highly rearranged and mutated cancer genomes present major challenges in the identification of pathogenetic events driving the cancer process. Here, we engineered lymphoma-prone mice with chromosomal instability to assess the utility of mouse models in cancer gene discovery and the extent of cross-species overlap in cancer-associated copy number aberrations. Integrating with targeted re-sequencing, our comparative oncogenomic studies efficiently identified FBXW7 and PTEN as commonly deleted or mutated tumor suppressors in human T-cell acute lymphoblastic leukemia/lymphoma (T-ALL). More generally, the murine cancers acquire widespread recurrent clonal amplifications and deletions targeting loci syntenic to alterations present in not only human T-ALL but also diverse tumors of hematopoietic, mesenchymal and epithelial types. These results thus support the view that murine and human tumors experience common biological processes driven by orthologous genetic events as they evolve towards a malignant phenotype. The highly concordant nature of genomic events encourages the use of genome unstable murine cancer models in the discovery of biologically relevant driver events in human cancer. Experiment Overall Design: 22 lymphoma samples from Atm-/-, mTerc-/-, p53-/- triple knock-out mice were analyzed. DNA from healthy mice of the same line was used as reference. Each sample was hybridized with dye-swap replica.
transcription profiling by array, unknown experiment type
Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers. 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. Nature 447(7147):966-71 (2007)