Dataset Information

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

ABSTRACT: 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 TCR?, TCR?, and TCR?), 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 TCR? corresponding to that of tumor cells, the majority of the samples presented multiple TCR?, TCR?, and TCR? 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 TCR? or TCR? 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.

SUBMITTER: Iyer A

PROVIDER: S-EPMC6457216 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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

Iyer Aishwarya A Hennessey Dylan D O'Keefe Sandra S Patterson Jordan J Wang Weiwei W Salopek Thomas T Wong Gane Ka-Shu GK Gniadecki Robert R

Blood advances 20190401 7

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. ...[more]

PMID: 30967393

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Project description:BackgroundA prospective, observational, US-based study (PROVe) used three questionnaires (Pruritus-VAS, Skindex-29, MF/SS-CTCL QoL) to assess quality of life in patients diagnosed with mycosis fungoides cutaneous T-cell lymphoma (MF-CTCL); however, none of these studies was provided with a preference-based algorithm yielding health state utility values (HSUVs).ObjectiveThis study aimed to assess the feasibility of deriving HSUVs from published mapping algorithms by comparing mapped utilities with the HSUVs reported in the MF-CTCL literature.MethodsWe searched PubMed, the School of Health and Related Research Health Utility Database (ScHARRHUD), and the Health Economics Research Centre (HERC) database of mapping studies (version 7.0) to identify any studies mapping Pruritus-VAS, Skindex-29, or MF/SS-CTCL QoL to a preference-based instrument (ideally, EQ-5D), and any studies assessing HSUVs in MF-CTCL. Two algorithms from a recent study that mapped Pruritus-VAS onto EQ-5D-3L were applied to the PROVe patient-level data. We performed multiple imputation to handle missing VAS data, calculated average mapped utilities in the whole sample, and compared them with relevant factors using the t-test and one-way analysis of variance (ANOVA).ResultsOverall, 298 patients provided 1441 Pruritus-VAS scores over a 2-year follow-up (1-21 visits per patient). The average mapped HSUVs ranged between 0.950 and 0.999 depending on the algorithm applied and imputation of missing data. In subgroup analysis, significant differences (p < 0.05) were observed according to age, race, and cancer stage. A few previous studies that collected HSUVs from MF-CTCL patients reported mean values of between 0.82 and 0.87 using time trade-off, 0.63 and 0.83 using EQ-5D, and 0.51 and 0.69 using the HUI3.ConclusionsThe HSUVs derived by applying published mapping algorithms to PROVe Pruritus-VAS data appeared largely overestimated if compared with the existing literature. More research is required to understand the applicability of existing mapping algorithms and to develop new mapping algorithms in MF-CTCL.

Dataset Information

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

Publications

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

Similar Datasets

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