Clonotypic heterogeneity in cutaneous T-cell lymphoma (mycosis fungoides) revealed by comprehensive whole-exome sequencing.

Authors:
Aishwarya Iyer
Aishwarya Iyer
Indian Institute of Science Education and Research Pune
India
Jordan Patterson
Jordan Patterson
University of Alberta
Weiwei Wang
Weiwei Wang
Tianjin Key Laboratory of Biomaterial Research
Germany
Gane Ka-Shu Wong
Gane Ka-Shu Wong
University of Alberta
Canada
Robert Gniadecki
Robert Gniadecki
Bispebjerg Hospital
Denmark

Blood Adv 2019 Apr;3(7):1175-1184

Division of Dermatology, Department of Medicine, and.

Mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma, is believed to represent a clonal expansion of a transformed skin-resident memory T cell. T-cell receptor (TCR) clonality (ie, identical sequences of rearranged TCRα, TCRβ, and TCRγ), the key premise of this hypothesis, has been difficult to document conclusively because malignant cells are not readily distinguishable from the tumor-infiltrating reactive lymphocytes that contribute to the TCR clonotypic repertoire of MF. Here, we have successfully adopted targeted whole-exome sequencing (WES) to identify the repertoire of rearranged TCR genes in tumor-enriched samples from patients with MF. Although some of the investigated MF biopsies had the expected frequency of monoclonal rearrangements of TCRγ corresponding to that of tumor cells, the majority of the samples presented multiple TCRγ, TCRα, and TCRβ clonotypes by WES. Our findings are compatible with the model in which the initial malignant transformation in MF does not occur in mature memory T cells but rather at the level of T-lymphocyte progenitors before TCRβ or TCRα rearrangements. We have also shown that WES can be combined with whole-transcriptome sequencing in the same sample, which enables comprehensive characterization of the TCR repertoire in relation to tumor content. WES/whole-transcriptome sequencing might be applicable to other types of T-cell lymphomas to determine clonal dominance and clonotypic heterogeneity in these malignancies.

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Source
http://www.bloodadvances.org/lookup/doi/10.1182/bloodadvance
Publisher Site
http://dx.doi.org/10.1182/bloodadvances.2018027482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457216PMC
April 2019
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References

(Supplied by CrossRef)
High detection rate of T-cell receptor beta chain rearrangements in T-cell lymphoproliferations by family specific polymerase chain reaction in combination with the GeneScan technique and DNA sequencing
Assaf et al.
Blood 2000

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