title: Heterogeneous abnormalities of CCND1 and RB1 in primary cutaneous T-Cell lymphomas suggesting impaired cell cycle control in disease pathogenesis.
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.
authors.affiliation: Skin Tumour Unit, St John's Institute of Dermatology, St Thomas' Hospital, King's College, London, UK. mxmayo@yahoo.co.uk
authors.forename: Xin
authors.initials: X
authors.lastname: Mao
authors.forename: Guy
authors.initials: G
authors.lastname: Orchard
authors.forename: Eric C
authors.initials: EC
authors.lastname: Vonderheid
authors.forename: Peter C
authors.initials: PC
authors.lastname: Nowell
authors.forename: Martine
authors.initials: M
authors.lastname: Bagot
authors.forename: Armand
authors.initials: A
authors.lastname: Bensussan
authors.forename: Robin
authors.initials: R
authors.lastname: Russell-Jones
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Young
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Whittaker
mesh_terms: D002467:Cell Nucleus / Q000737:chemistry / Q000235:genetics; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D019938:Cyclin D1 / Q000032:analysis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D017728:Lymphoma, Large-Cell, Anaplastic / Q000737:chemistry / Q000235:genetics; D016410:Lymphoma, T-Cell, Cutaneous / Q000737:chemistry / Q000235:genetics*; D008297:Male; D009182:Mycosis Fungoides / Q000737:chemistry / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D016160:Retinoblastoma Protein / Q000032:analysis / Q000235:genetics*; D012751:Sezary Syndrome / Q000737:chemistry / Q000235:genetics; D012878:Skin Neoplasms / Q000737:chemistry / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D016160:Retinoblastoma Protein; D019938:Cyclin D1