Enhancing diagnosis of T-cell lymphoma using non-recombined T-cell receptor sequences

Yi Lin Chen, Chung Liang Ho, Chen Yan Hung, Wan Li Chen, Chen Chang, Yi Hsin Hou, Jian Rong Chen, Pin Jun Chen, Nan Haw Chow, Wenya Huang, Ya Ting Hsu, Tsai Yun Chen, Tsunglin Liu

研究成果: Article同行評審

1 引文 斯高帕斯(Scopus)

摘要

Clonality assessment, which can detect neoplastic T cells by identifying the uniquely recombined T-cell receptor (TCR) genes, provides important support in the diagnosis of T-cell lymphoma (TCL). BIOMED-2 is the gold standard clonality assay and has proven to be effective in European TCL patients. However, we failed to prove its sensitivity in Taiwanese TCL patients, especially based on the TCRβ gene. To explore potential impact of genetic background in the BIOMED-2 test, we analyzed TCRβ sequences of 21 healthy individuals and two TCL patients. This analysis suggests that genetic variations in the BIOMED-2 primer sites could not explain the difference in sensitivity. The BIOMED-2 test results of the two TCL patients were positive and negative, respectively. Interestingly, a higher percentage (>81%) of non-recombined TCRβ sequences was observed in the test-negative patient than those of the test-positive patient and all healthy individuals (13~66%). The result suggests a new TCR target for enhancing TCL diagnosis. To further explore the hypothesis, we proposed a cost-effective digital PCR assay that quantifies the relative abundance of non-recombined TCRβ sequences containing a J2-2P~J2-3 segment. With the digital PCR assay, bone marrow specimens from TCL patients (n=9) showed a positive outcome (i.e., the relative abundance of the J2-2P~J2-3 sequences ≧5%), whereas non-TCL patients (n=6) gave a negative result. As five of nine TCL patients had a negative BIOMED-2 test result, the J2-2P~J2-3 sequences may improve TCL detection. This is the first report showing the capability of characterizing non-recombined TCR sequences as a supplementary strategy for the BIOMED-2 clonality test.

原文English
文章編號1014132
期刊Frontiers in Oncology
12
DOIs
出版狀態Published - 2022 12月 8

All Science Journal Classification (ASJC) codes

  • 腫瘤科
  • 癌症研究

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