Title | Assessment of T-cell receptor repertoire and clonal expansion in peripheral T-cell lymphoma using RNA-seq data. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Gong Q, Wang C, Zhang W, Iqbal J, Hu Y, Greiner TC, Cornish A, Kim J-H, Rabadan R, Abate F, Wang X, Inghirami GG, McKeithan TW, Chan WC |
Journal | Sci Rep |
Volume | 7 |
Issue | 1 |
Pagination | 11301 |
Date Published | 2017 09 12 |
ISSN | 2045-2322 |
Keywords | Clonal Evolution, Computational Biology, Gene Expression Profiling, High-Throughput Nucleotide Sequencing, Humans, Lymphoma, T-Cell, Peripheral, Mutation, Receptors, Antigen, T-Cell, Sequence Analysis, RNA, Transcriptome |
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. |
DOI | 10.1038/s41598-017-11310-0 |
Alternate Journal | Sci Rep |
PubMed ID | 28900149 |
PubMed Central ID | PMC5595876 |
Grant List | P20 GM103427 / GM / NIGMS NIH HHS / United States P20 GM103471 / GM / NIGMS NIH HHS / United States S10 RR027754 / RR / NCRR NIH HHS / United States P20 RR016469 / RR / NCRR NIH HHS / United States P30 CA036727 / CA / NCI NIH HHS / United States P20 RR018788 / RR / NCRR NIH HHS / United States P30 CA033572 / CA / NCI NIH HHS / United States P50 CA136411 / CA / NCI NIH HHS / United States |
Related Faculty:
Giorgio Inghirami, M.D.