Angioimmunoblastic T cell lymphoma: Novel molecular insights by mutation profiling

Ming Wang, Shaowei Zhang, Shih Sung Chuang, Margaret Ashton-Key, Eguzkine Ochoa, Niccolo Bolli, George Vassiliou, Zifen Gao, Ming Qing Du

Research output: Contribution to journalArticle

Abstract

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 (n = 6) and U.K. (n = 3). We confirmed frequent mutations in TET2 (9/9), DNMT3A (3/9), IDH2 (3/9), RHOA (3/9) and PLCG1 (2/9) as recently reported by others. More importantly, we identified mutations in TNFRSF21 (1/9), CCND3 (1/9) and 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 TET2 and 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 RHOA, PLCG1 and 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.

Original languageEnglish
Pages (from-to)17763-17770
Number of pages8
JournalOncotarget
Volume8
Issue number11
DOIs
Publication statusPublished - Jan 1 2017

Keywords

  • AITL
  • Oncogenic mechanism
  • Somatic mutation
  • WES

ASJC Scopus subject areas

  • Oncology

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    Wang, M., Zhang, S., Chuang, S. S., Ashton-Key, M., Ochoa, E., Bolli, N., Vassiliou, G., Gao, Z., & Du, M. Q. (2017). Angioimmunoblastic T cell lymphoma: Novel molecular insights by mutation profiling. Oncotarget, 8(11), 17763-17770. https://doi.org/10.18632/oncotarget.14846