The Value of T-Cell Receptor γ (TRG) Clonality Evaluation by Next-Generation Sequencing in Clinical Hematolymphoid Tissues

Objectives: To evaluate feasibility of assessing T-cell receptor γ (TRG) clonality by next-generation sequencing (NGS) in hematolymphoid tissues.

Methods: We evaluated TRG clonality using NGS and polymerase chain reaction (PCR) assays in blood, bone marrow, and formalin-fixed, paraffin-embedded tissues in 41 archived cases, including 21 benign cases with no history of any lymphoproliferative disorders (LPDs), 16 LPDs (nine mature T-cell neoplasms, seven mature B-cell neoplasms and immune dysregulation-associated LPDs), and four atypical LPDs from 22 females and 19 males with a median age of 58 (range, 9-87) years.

Results: (1) NGS analyzed TRG sequence and peak ratios, and it had a greater sensitivity than PCR. (2) NGS identified small clones, including biallelic or monoallelic, and minimum clonal percentages (range, ~2.4% to ~69%) within all T cells. (3) We provide our strategy and criteria for evaluating NGS results. (4) We describe every case, with definitive evaluation of TRG clonality in 100% cases by NGS.

Conclusions: TRG clonality evaluation by NGS provides greater clinical utility than PCR.