Next Article in Journal
The Giant HECT E3 Ubiquitin Ligase HERC1 Is Aberrantly Expressed in Myeloid Related Disorders and It Is a Novel BCR-ABL1 Binding Partner
Next Article in Special Issue
Potential Biomarkers for Treatment Response to the BCL-2 Inhibitor Venetoclax: State of the Art and Future Directions
Previous Article in Journal
Radiomics and Dosiomics for Predicting Local Control after Carbon-Ion Radiotherapy in Skull-Base Chordoma
Previous Article in Special Issue
Sequential Colocalization of ERa, PR, and AR Hormone Receptors Using Confocal Microscopy Enables New Insights into Normal Breast and Prostate Tissue and Cancers
Article

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

1
Department of Pathology, National University Hospital, National University Health System, Singapore 119074, Singapore
2
Lymphoma Genomic Translational Research Laboratory, Division of Cellular and Molecular Research, National Cancer Centre Singapore, Singapore 169610, Singapore
3
Cancer and Stem Cell Biology, Duke-NUS Medical School, Singapore 169857, Singapore
4
Singapore Immunology Network (SIgN), A*STAR (Agency for Science, Technology and Research), Singapore 138632, Singapore
5
Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119074, Singapore
6
Viva-NUS Centre for Translational Research in Acute Leukaemia, Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore
7
VIVA—University Children’s Cancer Centre, Khoo Teck Puat–National University Children’s Medical Institute, National University Hospital, National University Health System, Singapore 119074, Singapore
8
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore
9
Cancer Science Institute of Singapore, National University of Singapore, Singapore 117599, Singapore
10
Department of Pathology, Chi-Mei Medical Center, Tainan 71004, Taiwan
11
Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya 466-8560, Japan
12
Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya 464-0021, Japan
13
Department of Pathology, Aichi Medical University Hospital, Nagakute 480-1195, Japan
14
Department of Pathology, Tan Tock Seng Hospital, Singapore 308433, Singapore
15
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
16
Department of Pathology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
17
Department of Pathology, Singapore General Hospital, Singapore 169608, Singapore
18
Lymphoma Genomic Translational Research Laboratory, Division of Medical Oncology, National Cancer Centre Singapore, Singapore 169610, Singapore
19
Department of Hematology-Oncology, National University Cancer Institute Singapore, National University Hospital, National University Health System, Singapore 119074, Singapore
20
Tumor Immunology Unit, University of Palermo School of Medicine, 90134 Palermo, Italy
21
Genome Institute of Singapore, A*STAR (Agency for Science, Technology and Research), Singapore 138632, Singapore
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Lead contact.
Cancers 2021, 13(2), 340; https://doi.org/10.3390/cancers13020340
Received: 25 December 2020 / Accepted: 11 January 2021 / Published: 19 January 2021
T-cells defend the human body from pathogenic invasion via specific recognition by T-cell receptors (TCRs). The TCR genes undergo recombination (rearrangement) in a myriad of possible ways to generate different TCRs that can recognize a wide diversity of foreign antigens. However, in patients with T-cell lymphoma (TCL), a particular T-cell becomes malignant and proliferates, resulting in a population of genetically identical cells with same TCR rearrangement pattern. To help diagnose patients with TCL, a polymerase chain reaction (PCR)-based assay is currently used to determine if neoplastic cells in patient samples are of T-cell origin and bear identical (monoclonal) TCR rearrangement pattern. Herein, we report the application of a novel segmentation and copy number computation algorithm to accurately identify different TCR rearrangement patterns using data from the whole genome sequencing of patient materials. Our approach may improve the diagnostic accuracy of TCLs and can be similarly applied to the diagnosis of B-cell lymphomas.
T-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. View Full-Text
Keywords: whole genome sequencing; T-cell receptor; clonality; copy number variation analysis; T-cell lymphoma whole genome sequencing; T-cell receptor; clonality; copy number variation analysis; T-cell lymphoma
Show Figures

Figure 1

MDPI and ACS Style

Oon, M.L.; Lim, J.Q.; Lee, B.; Leong, S.M.; Soon, G.S.-T.; Wong, Z.W.; Lim, E.H.; Li, Z.; Yeoh, A.E.J.; Chen, S.; Ban, K.H.K.; Chung, T.-H.; Tan, S.-Y.; Chuang, S.-S.; Kato, S.; Nakamura, S.; Takahashi, E.; Ho, Y.-H.; Khoury, J.D.; Au-Yeung, R.K.H.; Cheng, C.-L.; Lim, S.-T.; Chng, W.-J.; Tripodo, C.; Rotzschke, O.; Ong, C.K.; Ng, S.-B. T-Cell Lymphoma Clonality by Copy Number Variation Analysis of T-Cell Receptor Genes. Cancers 2021, 13, 340. https://doi.org/10.3390/cancers13020340

AMA Style

Oon ML, Lim JQ, Lee B, Leong SM, Soon GS-T, Wong ZW, Lim EH, Li Z, Yeoh AEJ, Chen S, Ban KHK, Chung T-H, Tan S-Y, Chuang S-S, Kato S, Nakamura S, Takahashi E, Ho Y-H, Khoury JD, Au-Yeung RKH, Cheng C-L, Lim S-T, Chng W-J, Tripodo C, Rotzschke O, Ong CK, Ng S-B. T-Cell Lymphoma Clonality by Copy Number Variation Analysis of T-Cell Receptor Genes. Cancers. 2021; 13(2):340. https://doi.org/10.3390/cancers13020340

Chicago/Turabian Style

Oon, Ming L., Jing Q. Lim, Bernett Lee, Sai M. Leong, Gwyneth S.-T. Soon, Zi W. Wong, Evelyn H. Lim, Zhenhua Li, Allen E.J. Yeoh, Shangying Chen, Kenneth H.K. Ban, Tae-Hoon Chung, Soo-Yong Tan, Shih-Sung Chuang, Seiichi Kato, Shigeo Nakamura, Emiko Takahashi, Yong-Howe Ho, Joseph D. Khoury, Rex K.H. Au-Yeung, Chee-Leong Cheng, Soon-Thye Lim, Wee-Joo Chng, Claudio Tripodo, Olaf Rotzschke, Choon K. Ong, and Siok-Bian Ng. 2021. "T-Cell Lymphoma Clonality by Copy Number Variation Analysis of T-Cell Receptor Genes" Cancers 13, no. 2: 340. https://doi.org/10.3390/cancers13020340

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop