Condensin II mutation causes T-cell lymphoma through tissue-specific genome instability
| العنوان: | Condensin II mutation causes T-cell lymphoma through tissue-specific genome instability |
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| المؤلفون: | Karen Blyth, Shelagh Boyle, Milica Vukovic, Juan Carlos Acosta, Mark J. Arends, Kirsteen J. Campbell, Andrew J. Wood, Dinesh C. Soares, Bauke Ylstra, Gillian C.A. Taylor, Keerthi T. Chathoth, Wendy A. Bickmore, Núria Tarrats, David Read, Andrew P. Jackson, Jessica Woodward, David Jamieson, Daoud Sie, Kamil R. Kranc |
| المساهمون: | Pathology, CCA - Cancer biology |
| المصدر: | Genes and Development, 30(19), 2173-2186. Cold Spring Harbor Laboratory Press Woodward, J, Taylor, G C, Soares, D C, Boyle, S, Sie, D, Read, D, Chathoth, K, Vukovic, M, Tarrats, N, Jamieson, D, Campbell, K J, Blyth, K, Acosta, J C, Ylstra, B, Arends, M J, Kranc, K R, Jackson, A P, Bickmore, W A & Wood, A J 2016, ' Condensin II mutation causes T cell lymphoma through tissue-specific genome instability ', Genes and Development, vol. 30, no. 19, pp. 2173-2186 . https://doi.org/10.1101/gad.284562.116Test Woodward, J, Taylor, G C, Soares, D C, Boyle, S, Sie, D, Read, D, Chathoth, K, Vukovic, M, Tarrats, N, Jamieson, D, Campbell, K J, Blyth, K, Acosta, J C, Ylstra, B, Arends, M J, Kranc, K R, Jackson, A P, Bickmore, W A & Woods, A J 2016, ' Condensin II mutation causes T-cell lymphoma through tissue-specific genome instability ', Genes and Development, vol. 30, no. 19, pp. 2173-2186 . https://doi.org/10.1101/gad.284562.116Test |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Genome instability, Condensin, Mutation, Missense, lymphoma, macromolecular substances, Lymphoma, T-Cell, medicine.disease_cause, Genomic Instability, Chromosome segregation, Mice, 03 medical and health sciences, Condensin complex, Chromosome instability, Genetics, medicine, Animals, Mitosis, Cells, Cultured, Metaphase, Adenosine Triphosphatases, mitosis, Mutation, Thymocytes, biology, condensin, Thymus Neoplasms, genome instability, 3. Good health, Cell biology, DNA-Binding Proteins, 030104 developmental biology, Chromosome Structures, chromosome structure, Multiprotein Complexes, biology.protein, Female, Anaphase, Carcinogenesis, Research Paper, Developmental Biology |
| الوصف: | Chromosomal instability is a hallmark of cancer, but mitotic regulators are rarely mutated in tumors. Mutations in the condensin complexes, which restructure chromosomes to facilitate segregation during mitosis, are significantly enriched in cancer genomes, but experimental evidence implicating condensin dysfunction in tumorigenesis is lacking. We report that mice inheriting missense mutations in a condensin II subunit (Caph2nes) develop T-cell lymphoma. Before tumors develop, we found that the same Caph2 mutation impairs ploidy maintenance to a different extent in different hematopoietic cell types, with ploidy most severely perturbed at the CD4+CD8+ T-cell stage from which tumors initiate. Premalignant CD4+CD8+ T cells show persistent catenations during chromosome segregation, triggering DNA damage in diploid daughter cells and elevated ploidy. Genome sequencing revealed that Caph2 single-mutant tumors are near diploid but carry deletions spanning tumor suppressor genes, whereas P53 inactivation allowed Caph2 mutant cells with whole-chromosome gains and structural rearrangements to form highly aggressive disease. Together, our data challenge the view that mitotic chromosome formation is an invariant process during development and provide evidence that defective mitotic chromosome structure can promote tumorigenesis. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0890-9369 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1309b56f27b0467ccfd9f6ef79ff6b0aTest https://doi.org/10.1101/gad.284562.116Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1309b56f27b0467ccfd9f6ef79ff6b0a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 08909369 |
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