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

TitleAssessment of T-cell receptor repertoire and clonal expansion in peripheral T-cell lymphoma using RNA-seq data.
Publication TypeJournal Article
Year of Publication2017
AuthorsGong 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
JournalSci Rep
Volume7
Issue1
Pagination11301
Date Published2017 09 12
ISSN2045-2322
KeywordsClonal 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.

DOI10.1038/s41598-017-11310-0
Alternate JournalSci Rep
PubMed ID28900149
PubMed Central IDPMC5595876
Grant ListP20 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.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
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