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.
journal_name
Naturejournal_title
Natureauthors
Maser RS,Choudhury B,Campbell PJ,Feng B,Wong KK,Protopopov A,O'Neil J,Gutierrez A,Ivanova E,Perna I,Lin E,Mani V,Jiang S,McNamara K,Zaghlul S,Edkins S,Stevens C,Brennan C,Martin ES,Wiedemeyer R,Kabbarah O,Nogueidoi
10.1038/nature05886subject
Has Abstractpub_date
2007-06-21 00:00:00pages
966-71issue
7147eissn
0028-0836issn
1476-4687pii
nature05886journal_volume
447pub_type
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