Academic Journal
Angioimmunoblastic T cell lymphoma: novel molecular insights by mutation profiling
| العنوان: | Angioimmunoblastic T cell lymphoma: novel molecular insights by mutation profiling |
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| المؤلفون: | Wang, M, Zhang, S, Chuang, S-S, Ashton-Key, M, Ochoa, E, Bolli, N, Vassiliou, G, Gao, Z, Du, M-Q |
| بيانات النشر: | Impact Journals //doi.org/10.18632/oncotarget.14846 Oncotarget |
| سنة النشر: | 2017 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | AITL, WES, oncogenic mechanism, somatic mutation |
| الوصف: | Angioimmunoblastic T cell lymphoma (AITL) originates from follicular helper T-cells and is characterised by a polymorphic infiltrate with the neoplastic T-cells forming small clusters around the follicle and high endothelial venules. Despite the recent advances in its phenotypic characterisation, the genetics and molecular mechanisms underlying AITL are not fully understood. In the present study, we performed whole exome sequencing in 9 cases of AITL from Taiwan ($\textit{n}$ = 6) and U.K. ($\textit{n}$ = 3). We confirmed frequent mutations in $\textit{TET2}$ (9/9), $\textit{DNMT3A}$ (3/9), $\textit{IDH2}$ (3/9), $\textit{RHOA}$ (3/9) and $\textit{PLCG1}$ (2/9) as recently reported by others. More importantly, we identified mutations in $\textit{TNFRSF21}$ (1/9), $\textit{CCND3}$ (1/9) and $\textit{SAMSN1}$ (1/9), which are not yet seen or strongly implicated in the pathogenesis of AITL. Among the pathogenic mutations identified in AITL, mutations in DNA methylation regulators $\textit{TET2}$ and $\textit{DNMT3A}$ occur early in hematopoietic stem cells as shown by previous studies, and these genetic events enhance the self-renewal of hematopoietic stem cells, but are unlikely to have any major impact on T-cell differentiation. Mutations in $\textit{RHOA}$, $\textit{PLCG1}$ and $\textit{TNFRSF21}$ (DR6), which encode proteins critical for T-cell biology, most likely promote T-cell differentiation and malignant transformation, consequently generating the malignant phenotype. Our findings extend the molecular insights into the multistage development of AITL. ; The research was supported by grants from Kay Kendall Leukaemia Fund (KKL582), and Bloodwise, U.K. (13006). SZ was supported by a scholarship from the Master Hsingyun Cultural and Education Foundation. We thank Wenhan Deng for DNA preparation in some of the cases used in this study. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| Relation: | https://www.repository.cam.ac.uk/handle/1810/263427 |
| DOI: | 10.17863/CAM.8769 |
| الاتاحة: | https://www.repository.cam.ac.uk/handle/1810/263427 https://doi.org/10.17863/CAM.8769 |
| Rights: | Attribution 4.0 International ; http://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: | edsbas.26CB6F7F |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.8769 |
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