title: Amplification and overexpression of JUNB is associated with primary cutaneous T-cell lymphomas.
abstract: Primary cutaneous lymphomas (PCLs) represent a heterogeneous group of extranodal T- and B-cell malignancies. The underlying molecular pathogenesis of this malignancy remains unclear. This study aimed to characterize oncogene abnormalities in PCLs. Using genomic microarray, we detected oncogene copy number gains of RAF1 (3p25), CTSB (8p22), PAK1 (11q13), and JUNB (19p13) in 5 of 7 cases of mycosis fungoides (MF)/Sezary syndrome (SS) (71%), gains of FGFR1 (8p11), PTPN (20q13), and BCR (22q11) in 4 cases (57%), and gains of MYCL1 (1p34), PIK3CA (3q26), HRAS (11p15), MYBL2 (20q13), and ZNF217 (20q13) in 3 cases (43%). Amplification of JUNB was studied in 104 DNA samples from 78 PCL cases using real-time polymerase chain reaction. Twenty-four percent of cases, including 7 of 10 cases of primary cutaneous CD30(+) anaplastic large-cell lymphoma (C-ALCL), 4 of 14 MF, 4 of 22 SS, and 2 of 23 primary cutaneous B-cell lymphoma (PCBCL) showed amplification of JUNB, and high-level amplification of this oncogene was present in 3 C-ALCL and 2 MF cases. JUNB protein expression was analyzed in tissue sections from 69 PCL cases, and 44% of cases, consisting of 21 of 23 SS, 6 of 8 C-ALCL, 5 of 10 MF, and 9 of 21 PCBCL, demonstrated nuclear expression of JUNB by tumor cells. Overexpression of JUNB also was detected in 5 C-ALCL and 2 SS cases. These results have revealed, for the first time, amplification and expression patterns of JUNB in PCL, suggesting that JUNB may be critical in the pathogenesis of primary cutaneous T-cell lymphomas.
authors.affiliation: Skin Tumour Unit and Dermatopathology Department, St John's Institute of Dermatology, St Thomas' Hospital, London, United Kingdom. mxmayo@hotmail.com
authors.forename: Xin
authors.initials: X
authors.lastname: Mao
authors.forename: Guy
authors.initials: G
authors.lastname: Orchard
authors.forename: Debra M
authors.initials: DM
authors.lastname: Lillington
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: D004273:DNA, Neoplasm / Q000032:analysis; D005784:Gene Amplification; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics*; D009182:Mycosis Fungoides / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012751:Sezary Syndrome / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; D016755:Proto-Oncogene Proteins c-jun