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人类肿瘤标本外显子文件中的T细胞受体基因重组:T细胞受体-β VDJ重组的检测与膀胱癌良好的肿瘤学预后相关。

T cell receptor gene recombinations in human tumor specimen exome files: detection of T cell receptor-β VDJ recombinations associates with a favorable oncologic outcome for bladder cancer.

作者信息

Samy Mohammad D, Tong Wei Lue, Yavorski John M, Sexton Wade J, Blanck George

机构信息

Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Bd., Tampa, FL, 33612, USA.

Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.

出版信息

Cancer Immunol Immunother. 2017 Mar;66(3):403-410. doi: 10.1007/s00262-016-1943-1. Epub 2016 Dec 19.

Abstract

Understanding tumor-resident T cells is important for cancer prognosis and treatment options. Conventional, solid tumor specimen exome files can be searched directly for recombined T cell receptor (TcR)-α segments; RNASeq files can include TcR-β VDJ recombinations. To learn whether there are medically relevant uses of exome-based detection of TcR V(D)J recombinations in the tumor microenvironment, we searched cancer genome atlas and Moffitt Cancer Center, tumor specimen exome files for TcR-β, TcR-γ, and TcR-δ recombinations, for bladder and stomach cancer. We found that bladder cancer exomes with productive TcR-β recombinations had a significant association with No Subsequent Tumors and a positive response to drug treatments, with p < 0.004, p < 0.05, and p < 0.004, depending on the sample sets examined. We also discovered the opportunity to detect productive TcR-γ and TcR-δ recombinations in the tumor microenvironment, via the tumor specimen exome files.

摘要

了解肿瘤驻留T细胞对于癌症预后和治疗选择至关重要。可以直接在传统的实体瘤标本外显子文件中搜索重组的T细胞受体(TcR)-α片段;RNA测序文件可能包含TcR-β VDJ重组。为了了解基于外显子的肿瘤微环境中TcR V(D)J重组检测是否具有医学相关性,我们在癌症基因组图谱和莫菲特癌症中心搜索了膀胱癌和胃癌的肿瘤标本外显子文件,以查找TcR-β、TcR-γ和TcR-δ重组。我们发现,具有有效TcR-β重组的膀胱癌外显子与无后续肿瘤以及对药物治疗的阳性反应存在显著关联,根据所检查的样本集不同,p值分别小于0.004、小于0.05和小于0.004。我们还发现了通过肿瘤标本外显子文件在肿瘤微环境中检测有效TcR-γ和TcR-δ重组的机会。

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