Assessment of T-cell receptor repertoire and clonal expansion in peripheral T-cell lymphoma using RNA-seq data

作者:Gong, Qiang; Wang, Chao; Zhang, Weiwei; Iqbal, Javeed; Hu, Yang; Greiner, Timothy C.; Cornish, Adam; Kim, Jo-Heon; Rabadan, Raul; Abate, Francesco; Wang, Xin; Inghirami, Giorgio G.; McKeithan, Timothy W.; Chan, Wing C.*
来源:Scientific Reports, 2017, 7(1): 11301.
DOI:10.1038/s41598-017-11310-0

摘要

T-cell clonality of peripheral T-cell lymphoma (PTCL) is routinely evaluated with a PCR-based method using genomic DNA. However, there are limitations with this approach. The purpose of this study was to determine the utility of RNA-seq for assessing T-cell clonality and T-cell antigen receptor (TCR) repertoire of the neoplastic T-cells in 108 PTCL samples. TCR transcripts, including complementarity-determining region 3 (CDR3) sequences, were assessed. In normal T cells, the CDR3 sequences were extremely diverse, without any clonotype representing more than 2% of the overall TCR population. Dominant clones could be identified in 65 out of 76 PTCL cases (86%) with adequate TCR transcript expression. In monoclonal cases, the dominant clone varied between 11% and 99% of TCR beta transcripts. No unique V alpha or V beta usage was observed. Small T-cell clones were often observed in T-and NK-cell tumors in a percentage higher than observed in reactive conditions. gamma chain expression was very low in tumors expressing TCR alpha beta, but its expression level was high and clonality was detected in a TCR gamma delta expressing tumor. NK cell lymphoma (NKCL) did not express significant levels of TCR V beta or V gamma genes. RNA-seq is a useful tool for detecting and characterizing clonal TCR rearrangements in PTCL.