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Sci Rep. 2017 Sep 12;7(1):11301. doi: 10.1038/s41598-017-11310-0.

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

Author information

1
Department of Pathology, City of Hope National Medical Center, Duarte, 91010, CA, United States.
2
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, United States.
3
Department of Hematology, Shandong Provincial Hospital affiliated to Shandong University, Jinan, P.R. China.
4
Department of Pathology, Chonnam National University Medical School and Research Institute of Medical Sciences, Gwangju, South Korea.
5
Department of Biomedical Informatics, Columbia University, New York, NY, United States.
6
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, United States.
7
Department of Pathology, City of Hope National Medical Center, Duarte, 91010, CA, United States. jochan@coh.org.

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.

PMID:
28900149
PMCID:
PMC5595876
DOI:
10.1038/s41598-017-11310-0
[Indexed for MEDLINE]
Free PMC Article

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