Academic Journal
Genomic analyses reveal recurrent mutations in epigenetic modifiers and the JAK–STAT pathway in Sézary syndrome
| العنوان: | Genomic analyses reveal recurrent mutations in epigenetic modifiers and the JAK–STAT pathway in Sézary syndrome |
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| المؤلفون: | Kiel, Mark J., Sahasrabuddhe, Anagh A., Rolland, Delphine C. M., Velusamy, Thirunavukkarasu, Chung, Fuzon, Schaller, Matthew, Bailey, Nathanael G., Betz, Bryan L., Miranda, Roberto N., Porcu, Pierluigi, Byrd, John C., Medeiros, L. Jeffrey, Kunkel, Steven L., Bahler, David W., Lim, Megan S., Elenitoba-Johnson, Kojo S. J. |
| المصدر: | Nature Communications ; volume 6, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2015 |
| الوصف: | Sézary syndrome (SS) is an aggressive leukaemia of mature T cells with poor prognosis and limited options for targeted therapies. The comprehensive genetic alterations underlying the pathogenesis of SS are unknown. Here we integrate whole-genome sequencing ( n =6), whole-exome sequencing ( n =66) and array comparative genomic hybridization-based copy-number analysis ( n =80) of primary SS samples. We identify previously unknown recurrent loss-of-function aberrations targeting members of the chromatin remodelling/histone modification and trithorax families, including ARID1A in which functional loss from nonsense and frameshift mutations and/or targeted deletions is observed in 40.3% of SS genomes. We also identify recurrent gain-of-function mutations targeting PLCG1 (9%) and JAK1 , JAK3 , STAT3 and STAT5B ( JAK/STAT total ∼11%). Functional studies reveal sensitivity of JAK1-mutated primary SS cells to JAK inhibitor treatment. These results highlight the complex genomic landscape of SS and a role for inhibition of JAK/STAT pathways for the treatment of SS. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/ncomms9470 |
| الاتاحة: | http://dx.doi.org/10.1038/ncomms9470 https://www.nature.com/articles/ncomms9470.pdf https://www.nature.com/articles/ncomms9470 |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.57D2FFBE |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/ncomms9470 |
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