T-cell clonality assessment by next-generation sequencing improves detection sensitivity in mycosis fungoides

Kari E. Sufficool, Christina M. Lockwood, Haley J. Abel, Ian S. Hagemann, Jonathan A. Schumacher, Todd W. Kelley, Eric J. Duncavage

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Background T-cell receptor (TCR) clonality assessment is a principal diagnostic test in the management of mycosis fungoides (MF). However, current polymerase chain reaction-based methods may produce ambiguous results, often because of low abundance of clonal T lymphocytes, resulting in weak clonal peaks that cannot be size-resolved by contemporary capillary electrophoresis (CE). Objective We sought to determine if next-generation sequencing (NGS)-based detection has increased sensitivity for T-cell clonality over CE-based detection in MF. Methods Clonality was determined by an NGS-based method in which the TCR-γ variable region was polymerase chain reaction amplified and the products sequenced to establish the identity of rearranged variable and joining regions. Results Of the 35 MF cases tested, 29 (85%) showed a clonal T-cell rearrangement by NGS, compared with 15 (44%) by standard CE detection. Three patients with MF had follow-up testing that showed identical, clonal TCR sequences in subsequent skin biopsy specimens. Limitations Clonal T-cell populations have been described in benign conditions; evidence of clonality alone, by any method, is not sufficient for diagnosis. Conclusion TCR clonality assessment by NGS has superior sensitivity compared with CE-based detection. Further, NGS enables tracking of specific clones across multiple time points for more accurate identification of recurrent MF.

Original languageEnglish
Pages (from-to)228-236.e2
JournalJournal of the American Academy of Dermatology
Volume73
Issue number2
DOIs
StatePublished - Aug 1 2015

Keywords

  • T-cell clonality
  • T-cell receptor rearrangement
  • cutaneous T-cell lymphoma
  • molecular diagnostics
  • mycosis fungoides
  • next-generation sequencing

Fingerprint Dive into the research topics of 'T-cell clonality assessment by next-generation sequencing improves detection sensitivity in mycosis fungoides'. Together they form a unique fingerprint.

  • Cite this