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Title: T-Cell Lymphoma Clonality by Copy Number Variation Analysis of T-Cell Receptor Genes
Authors: Oon, Ming Liang
Lim, Jing Quan 
Lee, Bernett
Leong, Sai Mun 
Soon, Gwyneth Shook-Ting 
Wong, Zi Wei
Lim, Evelyn Huizi 
Li, Zhenhua 
Yeoh, Allen Eng Juh 
Chen, Shangying 
Ban, Kenneth Hon Kim 
Chung, Tae-Hoon 
Tan, Soo-Yong 
Chuang, Shih-Sung
Kato, Seiichi
Nakamura, Shigeo
Takahashi, Emiko
Ho, Yong-Howe
Khoury, Joseph D
Au-Yeung, Rex KH
Cheng, Chee-Leong 
Lim, Soon-Thye 
Chng, Wee-Joo 
Tripodo, Claudio
Rotzschke, Olaf
Ong, Choon Kiat 
Ng, Siok-Bian 
Keywords: Science & Technology
Life Sciences & Biomedicine
whole genome sequencing
T-cell receptor
copy number variation analysis
T-cell lymphoma
Issue Date: 1-Jan-2021
Publisher: MDPI
Citation: Oon, Ming Liang, Lim, Jing Quan, Lee, Bernett, Leong, Sai Mun, Soon, Gwyneth Shook-Ting, Wong, Zi Wei, Lim, Evelyn Huizi, Li, Zhenhua, Yeoh, Allen Eng Juh, Chen, Shangying, Ban, Kenneth Hon Kim, Chung, Tae-Hoon, Tan, Soo-Yong, Chuang, Shih-Sung, Kato, Seiichi, Nakamura, Shigeo, Takahashi, Emiko, Ho, Yong-Howe, Khoury, Joseph D, Au-Yeung, Rex KH, Cheng, Chee-Leong, Lim, Soon-Thye, Chng, Wee-Joo, Tripodo, Claudio, Rotzschke, Olaf, Ong, Choon Kiat, Ng, Siok-Bian (2021-01-01). T-Cell Lymphoma Clonality by Copy Number Variation Analysis of T-Cell Receptor Genes. CANCERS 13 (2). ScholarBank@NUS Repository.
Abstract: 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.
Source Title: CANCERS
ISSN: 20726694
DOI: 10.3390/cancers13020340
Appears in Collections:Staff Publications

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