Heterogeneous abnormalities of CCND1 and RB1 in primary cutaneous T-cell lymphomas suggesting impaired cell cycle control in disease pathogenesis

Xin Mao, Guy Orchard, Eric C. Vonderheid, Peter C. Nowell, Martine Bagot, Armand Bensussan, Robin Russell-Jones, Bryan D. Young, Sean J. Whittaker

Research output: Contribution to journalArticle

Abstract

Upregulation of cyclin D1/B-cell leukemia/lymphoma 1 (CCND1/BCL1) is present in most mantle cell lymphomas with the t(11;14)(q13;q32) translocation. However, little is known about the abnormalities of CCND1 and its regulator RB1 in primary cutaneous T-cell lymphomas (CTCL). We analyzed CCND and RB status in CTCL using fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), and Affymetrix expression microarray. FISH revealed loss of CCND1/BCL1 in five of nine Sézary syndrome (SS) cases but gain in two cases, and RB1 loss in four of seven SS cases. IHC showed absent CCND1/BCL1 expression in 18 of 30 SS, 10 of 23 mycosis fungoides (MF), and three of 10 primary cutaneous CD30+ anaplastic large-cell lymphoma (C-ALCL). Increased CCND1/BCL1 expression was seen in nine MF, seven C-ALCL, and six SS cases. Absent RB1 expression was detected in 8 of 12 MF and 7 of 9 SS cases, and raised RB1 expression in 7 of 8 C-ALCL. Affymetrix revealed increased gene expression of CCND2 in four of eight CTCL cases, CCND3 in three cases, and CDKN2C in two cases with a normal expression of CCND1 and RB1. These findings suggest heterogeneous abnormalities of CCND and RB in CTCL, in which dysregulated CCND and RB1 may lead to impaired cell cycle control.

Original languageEnglish (US)
Pages (from-to)1388-1395
Number of pages8
JournalJournal of Investigative Dermatology
Volume126
Issue number6
DOIs
StatePublished - Jun 2006
Externally publishedYes

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Cutaneous T-Cell Lymphoma
T-cells
Cyclin D1
B-Cell Leukemia
Cyclin B
Cell Cycle Checkpoints
B-Cell Lymphoma
Anaplastic Large-Cell Lymphoma
Mycosis Fungoides
Cells
Fluorescence In Situ Hybridization
Primary Cutaneous Anaplastic Large Cell Lymphoma
Immunohistochemistry
Mantle-Cell Lymphoma
Microarrays
Gene expression
Up-Regulation
Gene Expression

ASJC Scopus subject areas

  • Dermatology

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Heterogeneous abnormalities of CCND1 and RB1 in primary cutaneous T-cell lymphomas suggesting impaired cell cycle control in disease pathogenesis. / Mao, Xin; Orchard, Guy; Vonderheid, Eric C.; Nowell, Peter C.; Bagot, Martine; Bensussan, Armand; Russell-Jones, Robin; Young, Bryan D.; Whittaker, Sean J.

In: Journal of Investigative Dermatology, Vol. 126, No. 6, 06.2006, p. 1388-1395.

Research output: Contribution to journalArticle

Mao, X, Orchard, G, Vonderheid, EC, Nowell, PC, Bagot, M, Bensussan, A, Russell-Jones, R, Young, BD & Whittaker, SJ 2006, 'Heterogeneous abnormalities of CCND1 and RB1 in primary cutaneous T-cell lymphomas suggesting impaired cell cycle control in disease pathogenesis', Journal of Investigative Dermatology, vol. 126, no. 6, pp. 1388-1395. https://doi.org/10.1038/sj.jid.5700224
Mao, Xin ; Orchard, Guy ; Vonderheid, Eric C. ; Nowell, Peter C. ; Bagot, Martine ; Bensussan, Armand ; Russell-Jones, Robin ; Young, Bryan D. ; Whittaker, Sean J. / Heterogeneous abnormalities of CCND1 and RB1 in primary cutaneous T-cell lymphomas suggesting impaired cell cycle control in disease pathogenesis. In: Journal of Investigative Dermatology. 2006 ; Vol. 126, No. 6. pp. 1388-1395.
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AU - Mao, Xin

AU - Orchard, Guy

AU - Vonderheid, Eric C.

AU - Nowell, Peter C.

AU - Bagot, Martine

AU - Bensussan, Armand

AU - Russell-Jones, Robin

AU - Young, Bryan D.

AU - Whittaker, Sean J.

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AB - Upregulation of cyclin D1/B-cell leukemia/lymphoma 1 (CCND1/BCL1) is present in most mantle cell lymphomas with the t(11;14)(q13;q32) translocation. However, little is known about the abnormalities of CCND1 and its regulator RB1 in primary cutaneous T-cell lymphomas (CTCL). We analyzed CCND and RB status in CTCL using fluorescent in situ hybridization (FISH), immunohistochemistry (IHC), and Affymetrix expression microarray. FISH revealed loss of CCND1/BCL1 in five of nine Sézary syndrome (SS) cases but gain in two cases, and RB1 loss in four of seven SS cases. IHC showed absent CCND1/BCL1 expression in 18 of 30 SS, 10 of 23 mycosis fungoides (MF), and three of 10 primary cutaneous CD30+ anaplastic large-cell lymphoma (C-ALCL). Increased CCND1/BCL1 expression was seen in nine MF, seven C-ALCL, and six SS cases. Absent RB1 expression was detected in 8 of 12 MF and 7 of 9 SS cases, and raised RB1 expression in 7 of 8 C-ALCL. Affymetrix revealed increased gene expression of CCND2 in four of eight CTCL cases, CCND3 in three cases, and CDKN2C in two cases with a normal expression of CCND1 and RB1. These findings suggest heterogeneous abnormalities of CCND and RB in CTCL, in which dysregulated CCND and RB1 may lead to impaired cell cycle control.

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