Read the clonotype: Next-generation sequencing-based lymphocyte clonality analysis and perspectives for application

Patricia J T A Groenen1,2, Michiel van den Brand1,3, Leonie I Kroeze1,2

  • 1Department of Pathology, Radboud University Medical Center, Nijmegen, Netherlands.

Frontiers in Oncology
|February 27, 2023
PubMed

Insights

Next-generation sequencing (NGS) offers a more sensitive method for detecting immunoglobulin (IG) and T-cell receptor (TR) gene rearrangements. This advanced clonality testing aids in diagnosing lymphomas and other conditions.

Area of Science:

  • Hematology
  • Molecular Biology
  • Oncology

Background:

  • Clonality assessment of immunoglobulin (IG) and T-cell receptor (TR) genes is crucial for diagnosing B-cell and T-cell lymphomas.
  • Conventional fragment analysis methods for clonality testing have limitations in sensitivity and precision.

Purpose of the Study:

  • To develop and validate a next-generation sequencing (NGS)-based clonality assay for IG and TR gene rearrangements.
  • To enhance sensitivity and precision in clone detection and comparison compared to traditional methods.

Main Methods:

  • Development and validation of an NGS-based assay for IG heavy and kappa light chain, and TR gene rearrangements.
  • Application of the assay to formalin-fixed and paraffin-embedded tissues.

Main Results:

  • The NGS-based assay provides more sensitive detection of lymphocyte clones.
  • It allows for more precise comparison of clones than conventional fragment analysis.

Conclusions:

  • NGS-based clonality testing is a powerful tool for diagnosing lymphomas.
  • Potential applications include site-specific lymphoproliferations, immunodeficiency, autoimmune diseases, and monitoring primary and relapsed lymphomas.