Detection of Productively Rearranged TcR-α V-J Sequences in TCGA Exome Files: Implications for Tumor Immunoscoring and Recovery of Antitumor T-cells.
Detection of Productively Rearranged TcR-α V-J Sequences in TCGA Exome Files: Implications for Tumor Immunoscoring and Recovery of Antitumor T-cells.
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DOI：
10.4137/cin.s35784
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发表时间：
2016
影响因子：
2
通讯作者：
Blanck G
中科院分区：
文献类型：
--
作者：
Gill TR;Samy MD;Butler SN;Mauro JA;Sexton WJ;Blanck G
肿瘤免疫评分正在迅速成为判断预后的通用参数，从肿瘤中分离出的T细胞被用于体外扩增和给药，以促进抗肿瘤免疫反应。我们最近利用癌症基因组图谱的RNAseq数据来评估T细胞受体(TcR)的表达，特别是发现主要组织相容性II类(MHCII)和TcR-α恒定区表达水平之间存在很强的相关性。在本文中，我们描述了在TcGA外显子组文件中搜索TcR-αV区的结果，然后在V区数据集中搜索TcR-α-J区。原发癌和转移性乳腺癌样本文件都含有重组的TcR-αV-J区，读数从16到39不等，处于较高水平。在四次这样的V-J重排中，有三次是生产性重排。在莫菲特癌症中心患者的TCGA-膀胱癌、肺癌和卵巢癌数据集以及代表膀胱癌的外显子文件中也检测到重排的TcR-αV-J区域。这些结果表明，直接搜索常见的、常规的外显子组文件以寻找重排的TCR片段，可以在更复杂的免疫评分中发挥作用，或者在识别针对肿瘤抗原的特定T细胞克隆和TCR方面发挥作用。
Tumor immunoscoring is rapidly becoming a universal parameter of prognosis, and T-cells isolated from tumor masses are used for ex vivo amplification and readministration to patients to facilitate an antitumor immune response. We recently exploited the cancer genome atlas (TCGA) RNASeq data to assess T-cell receptor (TcR) expression and, in particular, discovered strong correlations between major histocompatibility class II (MHCII) and TcR-α constant region expression levels. In this article, we describe the results of searching TCGA exome files for TcR-α V-regions, followed by searching the V-region datasets for TcR-α-J regions. Both primary and metastatic breast cancer sample files contained recombined TcR-α V–J regions, ranging in read counts from 16–39, at the higher level. Among four such V–J rearrangements, three were productive rearrangements. Rearranged TcR-α V–J regions were also detected in TCGA–bladder cancer, –lung cancer, and –ovarian cancer datasets, as well as exome files representing bladder cancer, in Moffitt Cancer Center patients. These results suggest that a direct search of commonly available, conventional exome files for rearranged TcR segments could play a role in more sophisticated immunoscoring or in identifying particular T-cell clones and TcRs directed against tumor antigens.