Defining the clonality of peripheral T cell lymphomas using RNA-seq

Area of Science:

• Immunogenomics
• Molecular diagnostics
• Oncology

Background:

• Malignant T cells in T-cell lymphoma originate from a single clone, identifiable by a unique T cell receptor (TCR).
• Conventional methods for identifying T-cell clones have limitations in sensitivity and diagnostic resolution.

Purpose of the Study:

• To evaluate the utility of TCR sequencing from RNA-seq data for diagnosing peripheral T cell lymphomas (PTCLs).
• To compare the sensitivity and diagnostic capability of RNA-seq-based TCR analysis with conventional flow cytometry.

Main Methods:

• RNA-sequencing (RNA-seq) was performed on sorted T cell populations from 60 PTCL subjects.
• TCR alpha and beta chain sequences were extracted and quantified directly from RNA-seq data.
• TCR data was analyzed to identify dominant T cell clones and assess clonality.

Main Results:

• RNA-seq successfully identified a dominant T cell clone in 96% of samples with immunophenotypically aberrant populations.
• A dominant clone was detected by RNA-seq in 80% of samples lacking aberrant populations by flow cytometry.
• RNA-seq demonstrated increased sensitivity and diagnostic ability compared to flow cytometry for PTCL detection.

Conclusions:

• TCR information from RNA-seq provides a higher-resolution view of PTCLs than conventional methods.
• RNA-seq-based TCR analysis enhances the diagnostic capability for PTCL, even in cases with a normal immunophenotype.
• This method improves the detection of T cell clonality, aiding in PTCL diagnosis.