Germline cytotoxic lymphocytes defective mutations in Chinese patients with lymphoma

Chen,Xue; Zhang,Yang; Wang,Fang; Wang,Mangju; Teng,Wen; Lin,Yuehui; Han,Xiangping; Jin,Fangyuan; Xu,Yuanli; Cao,Panxiang; Fang,Jiancheng; Zhu,Ping; Tong,Chunrong; Liu,Hongxing

doi:10.3892/ol.2017.6898

Germline cytotoxic lymphocytes defective mutations in Chinese patients with lymphoma

Authors:
- Xue Chen
- Yang Zhang
- Fang Wang
- Mangju Wang
- Wen Teng
- Yuehui Lin
- Xiangping Han
- Fangyuan Jin
- Yuanli Xu
- Panxiang Cao
- Jiancheng Fang
- Ping Zhu
- Chunrong Tong
- Hongxing Liu
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Affiliations: Department of Pathology and Laboratory Medicine Division, Hebei Yanda Lu Daopei Hospital, Sanhe, Hebei 065201, P.R. China, Department of Hematology, Peking University First Hospital, Beijing 100034, P.R. China
Published online on: September 6, 2017 https://doi.org/10.3892/ol.2017.6898
Pages: 5249-5256
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Certain patients with lymphoma may harbor mutations in perforin 1 (PRF1), unc‑13 homolog D (UNC13D), syntaxin 11 (STX11), STXBP2 (syntaxin binding protein 2) or SH2 domain containing 1A (SH2D1A), which causes functional defects of cytotoxic lymphocytes. Data regarding the association between genetic defects and the development of lymphoma in Chinese patients are limited to date. In the present study, 90 patients with lymphoma were analyzed for UNC13D, PRF1, STXBP2, STX11, SH2D1A and X‑linked inhibitor of apoptosis. Mutations were observed in 24 (26.67%) patients; 16 patients exhibited mutations in UNC13D, 7 exhibited PRF1 mutations, and 1 exhibited monoallelic mutation in STX11. UNC13D c.2588G>A/p.G863D mutation was detected in 9 patients (10.00%) and in 4/210 controls (1.90%). This mutation was predicted to be pathogenic and it predominantly existed in the Chinese population. These findings suggest that impaired cytotoxic machinery may represent a predisposing factor for the development of lymphoma. Furthermore, these data describe a distinct mutation spectrum in Chinese patients with lymphoma, whereby UNC13D is the most frequently mutated gene. In addition, these findings suggest UNC13D c.2588G>A mutation is a founder mutation in Chinese patients.

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