TY - JOUR
T1 - T-cell clonality assessment by next-generation sequencing improves detection sensitivity in mycosis fungoides
AU - Sufficool, Kari E.
AU - Lockwood, Christina M.
AU - Abel, Haley J.
AU - Hagemann, Ian S.
AU - Schumacher, Jonathan A.
AU - Kelley, Todd W.
AU - Duncavage, Eric J.
N1 - Publisher Copyright:
© 2015 American Academy of Dermatology, Inc.
PY - 2015/8/1
Y1 - 2015/8/1
N2 - 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.
AB - 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.
KW - T-cell clonality
KW - T-cell receptor rearrangement
KW - cutaneous T-cell lymphoma
KW - molecular diagnostics
KW - mycosis fungoides
KW - next-generation sequencing
UR - http://www.scopus.com/inward/record.url?scp=84937524463&partnerID=8YFLogxK
U2 - 10.1016/j.jaad.2015.04.030
DO - 10.1016/j.jaad.2015.04.030
M3 - Article
C2 - 26048061
AN - SCOPUS:84937524463
SN - 0190-9622
VL - 73
SP - 228-236.e2
JO - Journal of the American Academy of Dermatology
JF - Journal of the American Academy of Dermatology
IS - 2
ER -