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Assessment of T-cell receptor repertoire and clonal expansion in peripheral T-cell lymphoma using RNA-seq data #MMPMID28900149
Gong Q; Wang C; Zhang W; Iqbal J; Hu Y; Greiner TC; Cornish A; Kim JH; Rabadan R; Abate F; Wang X; Inghirami GG; McKeithan TW; Chan WC
Sci Rep 2017[]; 7 (ä): ä PMID28900149show ga
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? transcripts. No unique V? or V? 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. ? chain expression was very low in tumors expressing TCR??, but its expression level was high and clonality was detected in a TCR?? expressing tumor. NK cell lymphoma (NKCL) did not express significant levels of TCR V? or V? genes. RNA-seq is a useful tool for detecting and characterizing clonal TCR rearrangements in PTCL.