Validation and interpretation of IGH and TCR clonality testing by Ion Torrent S5 NGS for diagnosis and disease monitoring in B and T cell cancers

Lindsay Lay, Brooke Stroup, Jacqueline E. Payton

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Cancers of B and T lymphocytes are the most common hematologic malignancies in the US. Molecular assays for assessing clonal rearrangements of the immunoglobulin receptor (IGH) and T-cell receptor (TCR), commonly referred to as B- and T-cell clonality, as well as determination of IGH somatic mutation status, enables improved diagnostic accuracy and disease monitoring. Here we describe validation of NGS LymphoTrack (IGH, TCRG, Invivoscribe, Inc) with Ion Torrent S5 sequencing, which employs a different sequencing chemistry and has not been previously reported for NGS clonality to our knowledge. We also demonstrate the concordance of clonality by LymphoTrack with S5 sequencing with other molecular methodologies and with clinical measurements of disease. We show that LymphoTrack with S5 sequencing identifies previously detected IGH and TCRG clonal sequences across matched biopsy specimens and clinical timepoints, enabling more precise and sensitive disease monitoring for B- and T-cell cancers compared to PCR fragment or capillary sequencing. In sum, our study demonstrates that the LymphoTrack assays with Ion Torrent S5 sequencing 1) can be used successfully for IGH and TCR clonality with reproducible results; 2) generates and quantifies clonal sequences to enable highly precise comparison of samples; 3) are substantially more sensitive than PCR fragment and return clonality results in specimens that failed PCR fragment assays; and 4) the TCRG assays are highly concordant with clinical and histopathologic diagnoses. Taken together, the LymphoTrack with Ion S5 NGS clonality assays offer a sensitive and precise method for diagnostic testing and disease monitoring in B- and T-cell cancers.

Original languageEnglish
Article numbere00191
JournalPractical Laboratory Medicine
Volume22
DOIs
StatePublished - Nov 2020

Keywords

  • Clonality
  • IGH
  • Leukemia
  • Lymphoma
  • NGS
  • Next-generation sequencing
  • TCR
  • Validation

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