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

J 2020

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

KOMKOV, Alexander; Anna MIROSHNICHENKOVA; Gaiaz NUGMANOV; Alexander POPOV; Mikhail POGORELYY et. al.

Basic information

Original name

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

Authors

Edition

British Journal of Haematology, England, Wiley-Blackwell, 2020, 0007-1048

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

30205 Hematology

Country of publisher

United States of America

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 6.998

RIV identification code

RIV/00216224:14740/20:00116416

Organization unit

Central European Institute of Technology

DOI

https://doi.org/10.1111/bjh.16230

UT WoS

000516520300019

EID Scopus

2-s2.0-85073999584

Keywords in English

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

Abstract

In the original language

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.

Cite

KOMKOV, Alexander; Anna MIROSHNICHENKOVA; Gaiaz NUGMANOV; Alexander POPOV; Mikhail POGORELYY; Eva ZAPLETALOVÁ; Hana JELINKOVA; Šárka POSPÍŠILOVÁ; Yuri LEBEDEV; Dmitriy CHUDAKOV; Yulia OLSHANSKAYA; Karla PLEVOVÁ; Michael MASCHAN and Ilgar MAMEDOV. High-throughput sequencing of T-cell receptor alpha chain clonal rearrangements at the DNA level in lymphoid malignancies. British Journal of Haematology. England: Wiley-Blackwell, 2020, vol. 188, No 5, p. 723-731. ISSN 0007-1048. Available from: https://doi.org/10.1111/bjh.16230.

@article{1678926,
   author = {Komkov, Alexander and Miroshnichenkova, Anna and Nugmanov, Gaiaz and Popov, Alexander and Pogorelyy, Mikhail and Zapletalová, Eva and Jelinkova, Hana and Pospíšilová, Šárka and Lebedev, Yuri and Chudakov, Dmitriy and Olshanskaya, Yulia and Plevová, Karla and Maschan, Michael and Mamedov, Ilgar},
   article_location = {England},
   article_number = {5},
   doi = {https://doi.org/10.1111/bjh.16230},
   keywords = {T-cell receptor alpha chain; clonal rearrangements; acute lymphoblastic leukaemia; lymphoproliferative disorders; high-throughput sequencing},
   language = {eng},
   issn = {0007-1048},
   journal = {British Journal of Haematology},
   title = {High-throughput sequencing of T-cell receptor alpha chain clonal rearrangements at the DNA level in lymphoid malignancies},
   url = {https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.16230},
   volume = {188},
   year = {2020}
}

TY  - JOUR
ID  - 1678926
AU  - Komkov, Alexander - Miroshnichenkova, Anna - Nugmanov, Gaiaz - Popov, Alexander - Pogorelyy, Mikhail - Zapletalová, Eva - Jelinkova, Hana - Pospíšilová, Šárka - Lebedev, Yuri - Chudakov, Dmitriy - Olshanskaya, Yulia - Plevová, Karla - Maschan, Michael - Mamedov, Ilgar
PY  - 2020
TI  - High-throughput sequencing of T-cell receptor alpha chain clonal rearrangements at the DNA level in lymphoid malignancies
JF  - British Journal of Haematology
VL  - 188
IS  - 5
SP  - 723-731
EP  - 723-731
PB  - Wiley-Blackwell
SN  - 00071048
KW  - T-cell receptor alpha chain
KW  - clonal rearrangements
KW  - acute lymphoblastic leukaemia
KW  - lymphoproliferative disorders
KW  - high-throughput sequencing
UR  - https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.16230
L2  - https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.16230
N2  - 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.
ER  -

KOMKOV, Alexander; Anna MIROSHNICHENKOVA; Gaiaz NUGMANOV; Alexander POPOV; Mikhail POGORELYY; Eva ZAPLETALOVÁ; Hana JELINKOVA; Šárka POSPÍŠILOVÁ; Yuri LEBEDEV; Dmitriy CHUDAKOV; Yulia OLSHANSKAYA; Karla PLEVOVÁ; Michael MASCHAN and Ilgar MAMEDOV. High-throughput sequencing of T-cell receptor alpha chain clonal rearrangements at the DNA level in lymphoid malignancies. \textit{British Journal of Haematology}. England: Wiley-Blackwell, 2020, vol.~188, No~5, p.~723-731. ISSN~0007-1048. Available from: https://doi.org/10.1111/bjh.16230.

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