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Prepublished online as a Blood First Edition Paper on October 3, 2002; DOI 10.1182/blood-2002-08-2434.
Submitted August 9, 2002
Accepted September 14, 2002
Amplification and overexpression of JUNB is associated with primary cutaneous T-cell lymphomas
Xin Mao*, Guy Orchard, Debra M Lillington, Robin Russell-Jones, Bryan D Young, and Sean J Whittaker
Skin Tumour Unit, St. John's Institute of Dermatology, St. Thomas' Hospital, London, United Kingdom; Medical Oncology Unit, Cancer Research UK, St. Bartholomew's Hospital, London, United Kingdom
Dermatopathology Department, St. John's Institute of Dermatology, St. Thomas' Hospital, London, United Kingdom
Cancer Research UK Medical Oncology Unit, St. Bartholomew's Hospital, London, United Kingdom
Skin Tumour Unit, St. John's Institute of Dermatology, St. Thomas' Hospital, London, United Kingdom
* Corresponding author; email: mxmayo{at}hotmail.com.
Primary cutaneous lymphomas (PCL) represent a heterogeneous group of extranodal T- and B-cell malignancies. The underlying molecular pathogenesis of this malignancy remains unclear. This study aimed to characterise oncogene abnormalities in PCL. 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 PCR. 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 analysed 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 tumour cells. Overexpression of JUNB was also 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.
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