T-cell clonality assessment by next-generation sequencing improves detection sensitivity in mycosis fungoides - 15/07/15
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.
Le texte complet de cet article est disponible en PDF.Key words : cutaneous T-cell lymphoma, molecular diagnostics, mycosis fungoides, next-generation sequencing, T-cell clonality, T-cell receptor rearrangement
Abbreviations used : CE, CTCL, MF, NGS, PCR, TCR
Plan
| This project was funded by the Washington University Department of Pathology and Immunology. |
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| Conflicts of interest: None declared. |
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| Reprints not available from the authors. |
Vol 73 - N° 2
P. 228 - août 2015 Retour au numéro
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