High-throughput sequencing of T-cell receptor alpha chain clonal rearrangements at the DNA level in lymphoid malignancies

Alexander Komkov, Anna Miroshnichenkova, Gaiaz Nugmanov, Alexander Popov, Mikhail Pogorelyy, Eva Zapletalova, Hana Jelinkova, Sarka Pospisilova, Yuri Lebedev, Dmitriy Chudakov, Yulia Olshanskaya, Karla Plevova, Michael Maschan, Ilgar Mamedov

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Rearrangements of T- and B-cell receptor (TCR and BCR) genes are useful markers for clonality assessment as well as for minimal residual disease (MRD) monitoring during the treatment of haematological malignancies. Currently, rearrangements of three out of four TCR and all BCR loci are used for this purpose. The fourth TCR gene, TRA, has not been used so far due to the lack of a method for its rearrangement detection in genomic DNA. Here we propose the first high-throughput sequencing based method for the identification of clonal TRA gene rearrangements at the DNA level. The method is based on target amplification of the rearranged TRA locus using an advanced multiplex polymerase chain reaction system and high-throughput sequencing, and has been tested on DNA samples from peripheral blood of healthy donors. Combinations of all functional V- and J-segments were detected, indicating the high sensitivity of the method. Additionally, we identified clonal TRA rearrangements in 57 out of 112 tested DNA samples of patients with various T-lineage lymphoproliferative disorders. The method fills the existing gap in utilizing the TRA gene for a wide range of studies, including clonality assessment, MRD monitoring and clonal evolution analysis in different lymphoid malignancies.

Original languageEnglish
Pages (from-to)723-731
Number of pages9
JournalBritish Journal of Haematology
Volume188
Issue number5
DOIs
Publication statusPublished - 1 Mar 2020
Externally publishedYes

Keywords

  • acute lymphoblastic leukaemia
  • clonal rearrangements
  • high-throughput sequencing
  • lymphoproliferative disorders
  • T-cell receptor alpha chain

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