title: Oncogenomic analysis of mycosis fungoides reveals major differences with Sezary syndrome.
abstract: Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma, is a malignancy of mature, skin-homing T cells. Sézary syndrome (Sz) is often considered to represent a leukemic phase of MF. In this study, the pattern of numerical chromosomal alterations in MF tumor samples was defined using array-based comparative genomic hybridization (CGH); simultaneously, gene expression was analyzed using microarrays. Highly recurrent chromosomal alterations in MF include gain of 7q36, 7q21-7q22 and loss of 5q13 and 9p21. The pattern characteristic of MF differs markedly from chromosomal alterations observed in Sz. Integration of data from array-based CGH and gene-expression analysis yielded several candidate genes with potential relevance in the pathogenesis of MF. We confirmed that the FASTK and SKAP1 genes, residing in loci with recurrent gain, demonstrated increased expression. The RB1 and DLEU1 tumor suppressor genes showed diminished expression associated with loss. In addition, it was found that the presence of chromosomal alterations on 9p21, 8q24, and 1q21-1q22 was associated with poor prognosis in patients with MF. This study provides novel insight into genetic alterations underlying MF. Furthermore, our analysis uncovered genomic differences between MF and Sz, which suggest that the molecular pathogenesis and therefore therapeutic requirements of these cutaneous T-cell lymphomas may be distinct.
authors.affiliation: Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands. rvandoorn@lumc.nl
authors.forename: Remco
authors.initials: R
authors.lastname: van Doorn
authors.forename: Marloes S
authors.initials: MS
authors.lastname: van Kester
authors.forename: Remco
authors.initials: R
authors.lastname: Dijkman
authors.forename: Maarten H
authors.initials: MH
authors.lastname: Vermeer
authors.forename: Aat A
authors.initials: AA
authors.lastname: Mulder
authors.forename: Karoly
authors.initials: K
authors.lastname: Szuhai
authors.forename: Jeroen
authors.initials: J
authors.lastname: Knijnenburg
authors.forename: Judith M
authors.initials: JM
authors.lastname: Boer
authors.forename: Rein
authors.initials: R
authors.lastname: Willemze
authors.forename: Cornelis P
authors.initials: CP
authors.lastname: Tensen
mesh_terms: D000368:Aged; D001706:Biopsy; D002869:Chromosome Aberrations; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009182:Mycosis Fungoides / Q000235:genetics* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012751:Sezary Syndrome / Q000235:genetics* / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology