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High-throughput sequencing of T-cell receptor alpha chain clonal rearrangements at the DNA level in lymphoid malignancies
A. Komkov, A. Miroshnichenkova, G. Nugmanov, A. Popov, M. Pogorelyy, E. Zapletalova, H. Jelinkova, S. Pospisilova, Y. Lebedev, D. Chudakov, Y. Olshanskaya, K. Plevova, M. Maschan, I. Mamedov,
Jazyk angličtina Země Velká Británie
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
17-75-10113
Russian Science Foundation - International
18-29-09132
Russian Foundation for Basic Research - International
18-315-20038
Russian Foundation for Basic Research - International
FNBr 65269705
Ministerstvo Zdravotnictví Ceské Republiky - International
PubMed
31587259
DOI
10.1111/bjh.16230
Knihovny.cz E-zdroje
- MeSH
- DNA nádorová genetika MeSH
- genová přestavba - alfa řetězec receptoru antigenů T-buněk * MeSH
- hematologické nádory genetika MeSH
- lidé MeSH
- lymfoproliferativní nemoci genetika MeSH
- multiplexová polymerázová řetězová reakce * MeSH
- vysoce účinné nukleotidové sekvenování * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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.
Citace poskytuje Crossref.org
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- $a Komkov, Alexander $u Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia. Laboratory of Cytogenetics and Molecular Genetics, Dmitry Rogachev National Medical and Research Centre of Paediatric Haematology, Oncology and Immunology, Moscow, Russia.
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- $a 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.
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