T-cell lymphoma clonality by copy number variation analysis of T-cell receptor genes

Ming Liang Oon, Jing Quan Lim, Bernett Lee, Sai Mun Leong, Gwyneth Shook Ting Soon, Zi Wei Wong, Evelyn Huizi Lim, Zhenhua Li, Allen Eng Juh Yeoh, Shangying Chen, Kenneth Hon Kim 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-YeungChee Leong Cheng, Soon Thye Lim, Wee Joo Chng, Claudio Tripodo, Olaf Rotzschke, Choon Kiat Ong, Siok Bian Ng

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article number340
Pages (from-to)1-17
Number of pages17
JournalCancers
Volume13
Issue number2
DOIs
StatePublished - Jan 2 2021
Externally publishedYes

Keywords

  • Clonality
  • Copy number variation analysis
  • T-cell lymphoma
  • T-cell receptor
  • Whole genome sequencing

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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