Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL)

Ulrik Ralfkiaer; Peter Hagedorn; Nannie Bangsgaard; Marianne B Løvendorf; Charlotte B Ahler; Lars Svensson; Katharina L Kopp; Marie T Vennegaard; Britt Lauenborg; John R Zibert; Thorbjørn Krejsgaard; Charlotte M Bonefeld; Rolf Søkilde; Lise M Gjerdrum; Tord Labuda; Anne-Merete Mathiesen; Kirsten Grønbaek; Mariusz A Wasik; Malgorzata Sokolowska-Wojdylo; Catherine Queille-Roussel; Robert Gniadecki; Elisabeth Ralfkiaer; Carsten Geisler; Thomas Litman; Anders Woetmann Andersen; Christian Glue; Mads A Røpke; Lone Skov; Niels Ødum

doi:10.1182/blood-2011-06-358382

Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL)

Ulrik Ralfkiaer, Peter Hagedorn, Nannie Bangsgaard, Marianne B Løvendorf, Charlotte B Ahler, Lars Svensson, Katharina L Kopp, Marie T Vennegaard, Britt Lauenborg, John R Zibert, Thorbjørn Krejsgaard, Charlotte M Bonefeld, Rolf Søkilde, Lise M Gjerdrum, Tord Labuda, Anne-Merete Mathiesen, Kirsten Grønbaek, Mariusz A Wasik, Malgorzata Sokolowska-Wojdylo, Catherine Queille-RousselRobert Gniadecki, Elisabeth Ralfkiaer, Carsten Geisler, Thomas Litman, Anders Woetmann Andersen, Christian Glue, Mads A Røpke, Lone Skov, Niels Ødum

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Abstract

Cutaneous T-cell lymphomas (CTCLs) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult because of a clinical and histologic resemblance to benign inflammatory skin diseases. To address whether microRNA (miRNA) profiling can discriminate CTCL from benign inflammation, we studied miRNA expression levels in 198 patients with CTCL, peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and dermatitis). Using microarrays, we show that the most induced (miR-326, miR-663b, and miR-711) and repressed (miR-203 and miR-205) miRNAs distinguish CTCL from benign skin diseases with > 90% accuracy in a training set of 90 samples and a test set of 58 blinded samples. These miRNAs also distinguish malignant and benign lesions in an independent set of 50 patients with PTL and skin inflammation and in experimental human xenograft mouse models of psoriasis and CTCL. Quantitative (q)RT-PCR analysis of 103 patients with CTCL and benign skin disorders validates differential expression of 4 of the 5 miRNAs and confirms previous reports on miR-155 in CTCL. A qRT-PCR-based classifier consisting of miR-155, miR-203, and miR-205 distinguishes CTCL from benign disorders with high specificity and sensitivity, and with a classification accuracy of 95%, indicating that miRNAs have a high diagnostic potential in CTCL.

Originalsprog	Engelsk
Tidsskrift	Blood
Vol/bind	118
Udgave nummer	22
Sider (fra-til)	5891-5900
Antal sider	10
ISSN	0006-4971
DOI	https://doi.org/10.1182/blood-2011-06-358382
Status	Udgivet - 24 nov. 2011

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10.1182/blood-2011-06-358382

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Ralfkiaer, U., Hagedorn, P., Bangsgaard, N., Løvendorf, M. B., Ahler, C. B., Svensson, L., Kopp, K. L., Vennegaard, M. T., Lauenborg, B., Zibert, J. R., Krejsgaard, T., Bonefeld, C. M., Søkilde, R., Gjerdrum, L. M., Labuda, T., Mathiesen, A.-M., Grønbaek, K., Wasik, M. A., Sokolowska-Wojdylo, M., ... Ødum, N. (2011). Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL). Blood, 118(22), 5891-5900. https://doi.org/10.1182/blood-2011-06-358382

Ralfkiaer, U, Hagedorn, P, Bangsgaard, N, Løvendorf, MB, Ahler, CB, Svensson, L, Kopp, KL, Vennegaard, MT, Lauenborg, B, Zibert, JR, Krejsgaard, T, Bonefeld, CM, Søkilde, R, Gjerdrum, LM, Labuda, T, Mathiesen, A-M, Grønbaek, K, Wasik, MA, Sokolowska-Wojdylo, M, Queille-Roussel, C, Gniadecki, R, Ralfkiaer, E, Geisler, C , Litman, T , Andersen, AW, Glue, C, Røpke, MA, Skov, L & Ødum, N 2011, 'Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL)', Blood, bind 118, nr. 22, s. 5891-5900. https://doi.org/10.1182/blood-2011-06-358382

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title = "Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL)",

abstract = "Cutaneous T-cell lymphomas (CTCLs) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult because of a clinical and histologic resemblance to benign inflammatory skin diseases. To address whether microRNA (miRNA) profiling can discriminate CTCL from benign inflammation, we studied miRNA expression levels in 198 patients with CTCL, peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and dermatitis). Using microarrays, we show that the most induced (miR-326, miR-663b, and miR-711) and repressed (miR-203 and miR-205) miRNAs distinguish CTCL from benign skin diseases with > 90% accuracy in a training set of 90 samples and a test set of 58 blinded samples. These miRNAs also distinguish malignant and benign lesions in an independent set of 50 patients with PTL and skin inflammation and in experimental human xenograft mouse models of psoriasis and CTCL. Quantitative (q)RT-PCR analysis of 103 patients with CTCL and benign skin disorders validates differential expression of 4 of the 5 miRNAs and confirms previous reports on miR-155 in CTCL. A qRT-PCR-based classifier consisting of miR-155, miR-203, and miR-205 distinguishes CTCL from benign disorders with high specificity and sensitivity, and with a classification accuracy of 95%, indicating that miRNAs have a high diagnostic potential in CTCL.",

author = "Ulrik Ralfkiaer and Peter Hagedorn and Nannie Bangsgaard and L{\o}vendorf, {Marianne B} and Ahler, {Charlotte B} and Lars Svensson and Kopp, {Katharina L} and Vennegaard, {Marie T} and Britt Lauenborg and Zibert, {John R} and Thorbj{\o}rn Krejsgaard and Bonefeld, {Charlotte M} and Rolf S{\o}kilde and Gjerdrum, {Lise M} and Tord Labuda and Anne-Merete Mathiesen and Kirsten Gr{\o}nbaek and Wasik, {Mariusz A} and Malgorzata Sokolowska-Wojdylo and Catherine Queille-Roussel and Robert Gniadecki and Elisabeth Ralfkiaer and Carsten Geisler and Thomas Litman and Andersen, {Anders Woetmann} and Christian Glue and R{\o}pke, {Mads A} and Lone Skov and Niels {\O}dum",

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doi = "10.1182/blood-2011-06-358382",

language = "English",

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pages = "5891--5900",

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TY - JOUR

T1 - Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL)

AU - Ralfkiaer, Ulrik

AU - Hagedorn, Peter

AU - Bangsgaard, Nannie

AU - Løvendorf, Marianne B

AU - Ahler, Charlotte B

AU - Svensson, Lars

AU - Kopp, Katharina L

AU - Vennegaard, Marie T

AU - Lauenborg, Britt

AU - Zibert, John R

AU - Krejsgaard, Thorbjørn

AU - Bonefeld, Charlotte M

AU - Søkilde, Rolf

AU - Gjerdrum, Lise M

AU - Labuda, Tord

AU - Mathiesen, Anne-Merete

AU - Grønbaek, Kirsten

AU - Wasik, Mariusz A

AU - Sokolowska-Wojdylo, Malgorzata

AU - Queille-Roussel, Catherine

AU - Gniadecki, Robert

AU - Ralfkiaer, Elisabeth

AU - Geisler, Carsten

AU - Litman, Thomas

AU - Andersen, Anders Woetmann

AU - Glue, Christian

AU - Røpke, Mads A

AU - Skov, Lone

AU - Ødum, Niels

PY - 2011/11/24

Y1 - 2011/11/24

N2 - Cutaneous T-cell lymphomas (CTCLs) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult because of a clinical and histologic resemblance to benign inflammatory skin diseases. To address whether microRNA (miRNA) profiling can discriminate CTCL from benign inflammation, we studied miRNA expression levels in 198 patients with CTCL, peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and dermatitis). Using microarrays, we show that the most induced (miR-326, miR-663b, and miR-711) and repressed (miR-203 and miR-205) miRNAs distinguish CTCL from benign skin diseases with > 90% accuracy in a training set of 90 samples and a test set of 58 blinded samples. These miRNAs also distinguish malignant and benign lesions in an independent set of 50 patients with PTL and skin inflammation and in experimental human xenograft mouse models of psoriasis and CTCL. Quantitative (q)RT-PCR analysis of 103 patients with CTCL and benign skin disorders validates differential expression of 4 of the 5 miRNAs and confirms previous reports on miR-155 in CTCL. A qRT-PCR-based classifier consisting of miR-155, miR-203, and miR-205 distinguishes CTCL from benign disorders with high specificity and sensitivity, and with a classification accuracy of 95%, indicating that miRNAs have a high diagnostic potential in CTCL.

AB - Cutaneous T-cell lymphomas (CTCLs) are the most frequent primary skin lymphomas. Nevertheless, diagnosis of early disease has proven difficult because of a clinical and histologic resemblance to benign inflammatory skin diseases. To address whether microRNA (miRNA) profiling can discriminate CTCL from benign inflammation, we studied miRNA expression levels in 198 patients with CTCL, peripheral T-cell lymphoma (PTL), and benign skin diseases (psoriasis and dermatitis). Using microarrays, we show that the most induced (miR-326, miR-663b, and miR-711) and repressed (miR-203 and miR-205) miRNAs distinguish CTCL from benign skin diseases with > 90% accuracy in a training set of 90 samples and a test set of 58 blinded samples. These miRNAs also distinguish malignant and benign lesions in an independent set of 50 patients with PTL and skin inflammation and in experimental human xenograft mouse models of psoriasis and CTCL. Quantitative (q)RT-PCR analysis of 103 patients with CTCL and benign skin disorders validates differential expression of 4 of the 5 miRNAs and confirms previous reports on miR-155 in CTCL. A qRT-PCR-based classifier consisting of miR-155, miR-203, and miR-205 distinguishes CTCL from benign disorders with high specificity and sensitivity, and with a classification accuracy of 95%, indicating that miRNAs have a high diagnostic potential in CTCL.

U2 - 10.1182/blood-2011-06-358382

DO - 10.1182/blood-2011-06-358382

M3 - Journal article

C2 - 21865341

SN - 0006-4971

VL - 118

SP - 5891

EP - 5900

JO - Blood

JF - Blood

IS - 22

ER -

Diagnostic microRNA profiling in cutaneous T-cell lymphoma (CTCL)

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