title: IRF4 gene rearrangements define a subgroup of CD30-positive cutaneous T-cell lymphoma: a study of 54 cases.
abstract: The identification of IFN regulatory factor 4 gene (IRF4) translocation in 8 out of 14 cases of cutaneous anaplastic large cell lymphomas (C-ALCLs) (Leukemia, 2009; 23(3):574-80) prompted us to study IRF4 locus status in different cutaneous T-cell lymphoma (CTCL) subtypes. Fluorescence in situ hybridization (FISH) was used with break-apart dual-color probes. Sixty samples from 54 patients were analyzed with 23 C-ALCL, 11 transformed mycosis fungoides (T-MF), 7 lymphomatoid papulosis (LyP), and 13 Sézary syndrome (SS) cases. IRF4 immunostaining was performed in 32 cases. We observed a split FISH signal pattern indicating a translocation at the IRF4 locus in 6 out of 23 C-ALCL (26%) and 2 out of 11 T-MF (18.2%) cases. Extra copies of the IRF4 locus were found in 4 out of 13 SS, 1 out of 11 T-MF, and 1 out of 23 C-ALCL cases, corresponding to either aneuploidy, chromosome 6 trisomy, or 6p partial gain. The IRF4 expression was not correlated with the presence of IRF4 alteration in C-ALCL or T-MF. Interestingly, IRF4 rearrangements define a subgroup of CD30-positive C-ALCL and T-MF cases. Conversely, T-MF cases with IRF4 rearrangements may correspond to the development of C-ALCL in MF patients and not to large cell transformation. Investigation of the biological pathways triggered by IRF4 rearrangements and/or expression in CTCL will provide a biological basis for IRF4-directed therapy.
authors.affiliation: Department of Histology and Molecular Pathology of Tumors, University Bordeaux 2, and Department of Dermatology, Hôpital Saint André, Bordeaux, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Pham-Ledard
authors.forename: Martina
authors.initials: M
authors.lastname: Prochazkova-Carlotti
authors.forename: Elodie
authors.initials: E
authors.lastname: Laharanne
authors.forename: Béatrice
authors.initials: B
authors.lastname: Vergier
authors.forename: Thomas
authors.initials: T
authors.lastname: Jouary
authors.forename: Marie
authors.initials: M
authors.lastname: Beylot-Barry
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Merlio
mesh_terms: D001706:Biopsy; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6; D053960:DNA Breaks; D005455:Fluorescent Antibody Technique; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000378:metabolism; D017730:Ki-1 Antigen / Q000378:metabolism; D016410:Lymphoma, T-Cell, Cutaneous / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009182:Mycosis Fungoides / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011003:Ploidies; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000099218:Interferon Regulatory Factor-4
chemical_list: D050835:Interferon Regulatory Factors; D017730:Ki-1 Antigen; D000099218:Interferon Regulatory Factor-4