Is It Time to Assess T Cell Clonality by Next-Generation Sequencing in Mature T Cell Lymphoid Neoplasms? A Scoping Review
<b>Background:</b> T cell clonality is commonly assessed in the diagnostic work-up of mature T cell lymphoid neoplasms. Although fragment-length polymerase chain reaction (FL-PCR) assays are most widely used, next-generation sequencing (NGS) of the TRG and TRB genes is increasingly being...
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| author | Rina Kansal |
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| description | <b>Background:</b> T cell clonality is commonly assessed in the diagnostic work-up of mature T cell lymphoid neoplasms. Although fragment-length polymerase chain reaction (FL-PCR) assays are most widely used, next-generation sequencing (NGS) of the TRG and TRB genes is increasingly being used to assess T cell clonality. <b>Objective:</b> The present work is a scoping review of studies that assessed T cell clonality by NGS for diagnostic purposes, including only studies that provided integrated clinicopathologic diagnoses in comparing FL-PCR and NGS assays to evaluate if it is preferable to use NGS-based assays for T cell clonality evaluation in diagnostic pathology. <b>Methods:</b> Papers published from 1992 to 3 August 2024 were searched in PubMed. Twenty-nine cohort studies and five instructive case reports, published from 2013–2024 from the USA, UK, Europe, and Australia that provided integrated clinicopathologic diagnoses and used NGS to evaluate T cell clonality in clinical specimens from patients with mature T cell neoplasms and related non-neoplastic and neoplastic diseases were included, with additional relevant studies. <b>Results:</b> Ten (34.4%) of the 29 cohorts included clinical samples from patients having various cutaneous and non-cutaneous T cell malignancies, related neoplasms, and reactive conditions; 2 (6.8%) studies focused on T cell prolymphocytic leukemia, 16 (55%) on cutaneous T cell lymphoma, and one on pediatric pityriasis lichenoides. Eleven (38%) of the 29 cohort studies compared NGS with FL-PCR assays in 908 clinical samples. Eight (72.7%) of the 11 studies compared TRG FL-PCR with TRG NGS (<i>n</i> = 5), TRB NGS (<i>n</i> = 2), and TRG NGS and TRB NGS (<i>n</i> = 1); the remaining three compared EuroClonality/BIOMED-2 FL-PCR (TRG and TRB) with TRG NGS (<i>n</i> = 1), TRB NGS (<i>n</i> = 1), and the EuroClonality-NGS DNA capture assay (<i>n</i> = 1). TRB NGS was used in 16 (55%) of 29, TRG NGS in 6 (20.6%) of 29, and both TRG and TRB NGS in 7 (24%) of 29. Two (6.8%) of the 29 studies compared TRB NGS with flow cytometric immunophenotyping assays for Vβ and T cell receptor β constant region 1. One additional study compared long-read sequencing with NGS for TRG and TRB rearrangements. <b>Conclusions:</b> NGS is highly specific and sensitive for assessing T cell clonality. NGS precisely tracks unique rearranged sequences, which FL-PCR cannot. NGS findings for clonality must be interpreted in the context of all clinicopathologic and immunophenotypic findings, like FL-PCR. With such interpretations, NGS is much preferable to FL-PCR for evaluating T cell clonality for diagnostic purposes. It is necessary to reduce costs, increase accessibility, and educate providers about NGS for clonality evaluation. TRB NGS has been primarily assessed in the peripheral blood and skin, whereas TRG NGS has also been evaluated in formalin-fixed and non-cutaneous fresh lymphoid tissues. TRG NGS performed better than TRB NGS in comparative studies. |
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| spelling | doaj-art-5e2f4f2eb9e84ee8a90a2ebeb89c3a1b2025-08-20T03:43:34ZengMDPI AGJournal of Molecular Pathology2673-52612025-01-0161210.3390/jmp6010002Is It Time to Assess T Cell Clonality by Next-Generation Sequencing in Mature T Cell Lymphoid Neoplasms? A Scoping ReviewRina Kansal0Molecular Oncology and Genetics, Diagnostic Laboratories, Versiti Blood Center of Wisconsin, Milwaukee, WI 53233, USA<b>Background:</b> T cell clonality is commonly assessed in the diagnostic work-up of mature T cell lymphoid neoplasms. Although fragment-length polymerase chain reaction (FL-PCR) assays are most widely used, next-generation sequencing (NGS) of the TRG and TRB genes is increasingly being used to assess T cell clonality. <b>Objective:</b> The present work is a scoping review of studies that assessed T cell clonality by NGS for diagnostic purposes, including only studies that provided integrated clinicopathologic diagnoses in comparing FL-PCR and NGS assays to evaluate if it is preferable to use NGS-based assays for T cell clonality evaluation in diagnostic pathology. <b>Methods:</b> Papers published from 1992 to 3 August 2024 were searched in PubMed. Twenty-nine cohort studies and five instructive case reports, published from 2013–2024 from the USA, UK, Europe, and Australia that provided integrated clinicopathologic diagnoses and used NGS to evaluate T cell clonality in clinical specimens from patients with mature T cell neoplasms and related non-neoplastic and neoplastic diseases were included, with additional relevant studies. <b>Results:</b> Ten (34.4%) of the 29 cohorts included clinical samples from patients having various cutaneous and non-cutaneous T cell malignancies, related neoplasms, and reactive conditions; 2 (6.8%) studies focused on T cell prolymphocytic leukemia, 16 (55%) on cutaneous T cell lymphoma, and one on pediatric pityriasis lichenoides. Eleven (38%) of the 29 cohort studies compared NGS with FL-PCR assays in 908 clinical samples. Eight (72.7%) of the 11 studies compared TRG FL-PCR with TRG NGS (<i>n</i> = 5), TRB NGS (<i>n</i> = 2), and TRG NGS and TRB NGS (<i>n</i> = 1); the remaining three compared EuroClonality/BIOMED-2 FL-PCR (TRG and TRB) with TRG NGS (<i>n</i> = 1), TRB NGS (<i>n</i> = 1), and the EuroClonality-NGS DNA capture assay (<i>n</i> = 1). TRB NGS was used in 16 (55%) of 29, TRG NGS in 6 (20.6%) of 29, and both TRG and TRB NGS in 7 (24%) of 29. Two (6.8%) of the 29 studies compared TRB NGS with flow cytometric immunophenotyping assays for Vβ and T cell receptor β constant region 1. One additional study compared long-read sequencing with NGS for TRG and TRB rearrangements. <b>Conclusions:</b> NGS is highly specific and sensitive for assessing T cell clonality. NGS precisely tracks unique rearranged sequences, which FL-PCR cannot. NGS findings for clonality must be interpreted in the context of all clinicopathologic and immunophenotypic findings, like FL-PCR. With such interpretations, NGS is much preferable to FL-PCR for evaluating T cell clonality for diagnostic purposes. It is necessary to reduce costs, increase accessibility, and educate providers about NGS for clonality evaluation. TRB NGS has been primarily assessed in the peripheral blood and skin, whereas TRG NGS has also been evaluated in formalin-fixed and non-cutaneous fresh lymphoid tissues. TRG NGS performed better than TRB NGS in comparative studies.https://www.mdpi.com/2673-5261/6/1/2antigen receptorsT cellsgene rearrangementhigh-throughput DNA sequencingpolymerase chain reactionT cell lymphoma |
| spellingShingle | Rina Kansal Is It Time to Assess T Cell Clonality by Next-Generation Sequencing in Mature T Cell Lymphoid Neoplasms? A Scoping Review Journal of Molecular Pathology antigen receptors T cells gene rearrangement high-throughput DNA sequencing polymerase chain reaction T cell lymphoma |
| title | Is It Time to Assess T Cell Clonality by Next-Generation Sequencing in Mature T Cell Lymphoid Neoplasms? A Scoping Review |
| title_full | Is It Time to Assess T Cell Clonality by Next-Generation Sequencing in Mature T Cell Lymphoid Neoplasms? A Scoping Review |
| title_fullStr | Is It Time to Assess T Cell Clonality by Next-Generation Sequencing in Mature T Cell Lymphoid Neoplasms? A Scoping Review |
| title_full_unstemmed | Is It Time to Assess T Cell Clonality by Next-Generation Sequencing in Mature T Cell Lymphoid Neoplasms? A Scoping Review |
| title_short | Is It Time to Assess T Cell Clonality by Next-Generation Sequencing in Mature T Cell Lymphoid Neoplasms? A Scoping Review |
| title_sort | is it time to assess t cell clonality by next generation sequencing in mature t cell lymphoid neoplasms a scoping review |
| topic | antigen receptors T cells gene rearrangement high-throughput DNA sequencing polymerase chain reaction T cell lymphoma |
| url | https://www.mdpi.com/2673-5261/6/1/2 |
| work_keys_str_mv | AT rinakansal isittimetoassesstcellclonalitybynextgenerationsequencinginmaturetcelllymphoidneoplasmsascopingreview |