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Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers
Open accessAbstract
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.
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“Unlike classical balanced translocations, non-reciprocal translocations lead to copy number changes of the genes residing near the translocation breakage-rearrangement point (105).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [105]
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Metadata
- Authors
- Maser, R. S., Choudhury, B., Campbell, P. J., Feng, B., Wong, K.-K., 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, E. S., Wiedemeyer, R., Kabbarah, O., Nogueira, C., Histen, G., Aster, J., Mansour, M., Duke, V., Foroni, L., Fielding, A. K., Goldstone, A. H., Rowe, J. M., Wang, Y. A., Look, A. T., Stratton, M. R., Chin, L., Futreal, P. A., & DePinho, R. A.
- Affiliations
- Dana-Farber Cancer Institute (US)
- Wellcome Sanger Institute (GB)
- Agilent Technologies (United States) (US)
- Memorial Sloan Kettering Cancer Center (US)
- The Royal Free Hospital (GB)
- University College London (GB)
- Technion – Israel Institute of Technology (IL)
- Harvard University (US)
- Corresponding author
- DePinho, Ronald A.
- ORCID
- Choudhury, Bhudipa
- Campbell, Peter J.
- Feng, Bin
- Wong, Kwok-Kin
- Protopopov, Alexei
- O’Neil, Jennifer
- Ivanova, Elena
- Lin, Eric
- Jiang, Shan
- Edkins, Sarah
- Brennan, Cameron
- Martin, Eric S.
- Kabbarah, Omar
- Nogueira, Cristina
- Aster, Jon
- Mansour, Marc
- Fielding, Adele K.
- Goldstone, Anthony H.
- Rowe, Jacob M.
- Look, A. Thomas
- Stratton, Michael R.
- Futreal, P. Andrew
- DePinho, Ronald A.
- Venue
- Nature
- Published
- 2007-05-21
- Volume
- 447
- Issue
- 7147
- Pages
- 966-971
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2714968
- OpenAlex
- W1982767015
- Cited by
- 377
- References
- 50
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 8 · 2023: 8 · 2022: 8 · 2021: 5 · 2020: 11 · 2019: 6 · 2018: 12 · 2017: 16 · 2016: 17 · 2015: 21 · 2014: 25 · 2013: 34 · 2012: 32
- FWCI
- 15.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- Damon Runyon Cancer Research Foundation
- Wellcome Trust (077012, 088340)
- Kay Kendall Leukaemia Fund
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- chromosomal instability, mouse lymphoma model, T-cell acute lymphoblastic lymphoma, FBXW7, PTEN, notches, copy number alterations, genomic instability, driver mutations, tumor evolution, syntenic loci
- MeSH terms
- Animals, Chromosome Aberrations, Humans, Leukemia-Lymphoma, Adult T-Cell, Lymphoma, T-Cell, Genome, Conserved Sequence, Synteny, Chromosomal Instability, PTEN Phosphohydrolase, Mice
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