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Article: T-Cell Lymphoma Clonality by Copy Number Variation Analysis of T-Cell Receptor Genes

TitleT-Cell Lymphoma Clonality by Copy Number Variation Analysis of T-Cell Receptor Genes
Authors
Keywordswhole genome sequencing
T-cell receptor
clonality
copy number variation analysis
T-cell lymphoma
Issue Date2021
PublisherMDPI AG. The Journal's web site is located at http://www.mdpi.com/journal/cancers/
Citation
Cancers, 2021, v. 13 n. 2, p. article no. 340 How to Cite?
AbstractT-cell lymphomas arise from a single neoplastic clone and exhibit identical patterns of deletions in T-cell receptor (TCR) genes. Whole genome sequencing (WGS) data represent a treasure trove of information for the development of novel clinical applications. However, the use of WGS to identify clonal T-cell proliferations has not been systematically studied. In this study, based on WGS data, we identified monoclonal rearrangements (MRs) of T-cell receptors (TCR) genes using a novel segmentation algorithm and copy number computation. We evaluated the feasibility of this technique as a marker of T-cell clonality using T-cell lymphomas (TCL, n = 44) and extranodal NK/T-cell lymphomas (ENKTLs, n = 20), and identified 98% of TCLs with one or more TCR gene MRs, against 91% detected using PCR. TCR MRs were absent in all ENKTLs and NK cell lines. Sensitivity-wise, this platform is sufficiently competent, with MRs detected in the majority of samples with tumor content under 25% and it can also distinguish monoallelic from biallelic MRs. Understanding the copy number landscape of TCR using WGS data may engender new diagnostic applications in hematolymphoid pathology, which can be readily adapted to the analysis of B-cell receptor loci for B-cell clonality determination.
Persistent Identifierhttp://hdl.handle.net/10722/304333
ISSN
2023 Impact Factor: 4.5
2023 SCImago Journal Rankings: 1.391
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorOon, ML-
dc.contributor.authorLim, JQ-
dc.contributor.authorLee, B-
dc.contributor.authorLeong, SM-
dc.contributor.authorSoon, GST-
dc.contributor.authorWong, ZW-
dc.contributor.authorLim, EH-
dc.contributor.authorLi, Z-
dc.contributor.authorYeoh, AEJ-
dc.contributor.authorChen, S-
dc.contributor.authorBan, KHK-
dc.contributor.authorChung, TH-
dc.contributor.authorTan, SY-
dc.contributor.authorChuang, SS-
dc.contributor.authorKato, S-
dc.contributor.authorNakamura, S-
dc.contributor.authorTakahashi, E-
dc.contributor.authorHo, YH-
dc.contributor.authorKhoury, JD-
dc.contributor.authorAu Yeung, RKH-
dc.contributor.authorCheng, CL-
dc.contributor.authorLim, ST-
dc.contributor.authorChng, WJ-
dc.contributor.authorTripodo, C-
dc.contributor.authorRotzchke, O-
dc.contributor.authorOng, CK-
dc.contributor.authorNg, SB-
dc.date.accessioned2021-09-23T08:58:34Z-
dc.date.available2021-09-23T08:58:34Z-
dc.date.issued2021-
dc.identifier.citationCancers, 2021, v. 13 n. 2, p. article no. 340-
dc.identifier.issn2072-6694-
dc.identifier.urihttp://hdl.handle.net/10722/304333-
dc.description.abstractT-cell lymphomas arise from a single neoplastic clone and exhibit identical patterns of deletions in T-cell receptor (TCR) genes. Whole genome sequencing (WGS) data represent a treasure trove of information for the development of novel clinical applications. However, the use of WGS to identify clonal T-cell proliferations has not been systematically studied. In this study, based on WGS data, we identified monoclonal rearrangements (MRs) of T-cell receptors (TCR) genes using a novel segmentation algorithm and copy number computation. We evaluated the feasibility of this technique as a marker of T-cell clonality using T-cell lymphomas (TCL, n = 44) and extranodal NK/T-cell lymphomas (ENKTLs, n = 20), and identified 98% of TCLs with one or more TCR gene MRs, against 91% detected using PCR. TCR MRs were absent in all ENKTLs and NK cell lines. Sensitivity-wise, this platform is sufficiently competent, with MRs detected in the majority of samples with tumor content under 25% and it can also distinguish monoallelic from biallelic MRs. Understanding the copy number landscape of TCR using WGS data may engender new diagnostic applications in hematolymphoid pathology, which can be readily adapted to the analysis of B-cell receptor loci for B-cell clonality determination.-
dc.languageeng-
dc.publisherMDPI AG. The Journal's web site is located at http://www.mdpi.com/journal/cancers/-
dc.relation.ispartofCancers-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectwhole genome sequencing-
dc.subjectT-cell receptor-
dc.subjectclonality-
dc.subjectcopy number variation analysis-
dc.subjectT-cell lymphoma-
dc.titleT-Cell Lymphoma Clonality by Copy Number Variation Analysis of T-Cell Receptor Genes-
dc.typeArticle-
dc.identifier.emailAu Yeung, RKH: rex.auyeung@hku.hk-
dc.identifier.authorityAu Yeung, RKH=rp01877-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3390/cancers13020340-
dc.identifier.pmid33477749-
dc.identifier.pmcidPMC7832336-
dc.identifier.scopuseid_2-s2.0-85099973454-
dc.identifier.hkuros325597-
dc.identifier.volume13-
dc.identifier.issue2-
dc.identifier.spagearticle no. 340-
dc.identifier.epagearticle no. 340-
dc.identifier.isiWOS:000611099200001-
dc.publisher.placeSwitzerland-

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