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

Qiang Gong, Chao Wang, Weiwei Zhang, Javeed Iqbal, Yang Hu, Timothy C. Greiner, Adam Cornish, Jo Heon Kim, Raul Rabadan, Francesco Abate, Xin Wang, Giorgio G. Inghirami, Timothy W. McKeithan, Wing C. Chan

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12 Scopus citations

Abstract

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 TCRβ transcripts. No unique Vα or Vβ 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. γ chain expression was very low in tumors expressing TCRαβ, but its expression level was high and clonality was detected in a TCRγδ expressing tumor. NK cell lymphoma (NKCL) did not express significant levels of TCR Vβ or Vγ genes. RNA-seq is a useful tool for detecting and characterizing clonal TCR rearrangements in PTCL.

Original languageEnglish (US)
Article number11301
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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    Gong, Q., Wang, C., Zhang, W., Iqbal, J., Hu, Y., Greiner, T. C., Cornish, A., Kim, J. H., Rabadan, R., Abate, F., Wang, X., Inghirami, G. G., McKeithan, T. W., & Chan, W. C. (2017). Assessment of T-cell receptor repertoire and clonal expansion in peripheral T-cell lymphoma using RNA-seq data. Scientific reports, 7(1), [11301]. https://doi.org/10.1038/s41598-017-11310-0