title: Frequent fusion of the CRTC1 and MAML2 genes in clear cell variants of cutaneous hidradenomas.
abstract: Fusion of the CREB regulated transcription coactivator CRTC1 (a.k.a. MECT1, TORC1, or WAMTP1) to the Notch coactivator MAML2 is a characteristic feature of low-grade mucoepidermoid carcinomas of salivary and bronchial glands. The CRTC1-MAML2 fusion protein acts by inducing transcription of cAMP/CREB target genes, and this activity is crucial for the transforming properties of the protein. Here we show that the CRTC1-MAML2 gene fusion is also frequent in benign hidradenomas of the skin. FISH and RT-PCR analyses revealed that hidradenomas are genetically heterogeneous, and that 10 of the 20 tumors analyzed (50%) contained the CRTC1-MAML2 gene fusion and expressed the resulting fusion transcript. Immunohistochemical analysis demonstrated expression of the fusion protein in the majority of tumor cells, including clear cells, poroid cells, and cells with epidermoid and ductal differentiation. In addition, we could show that all fusion-positive tumors were morphologically distinguished by the presence of more or less abundant areas of clear cells whereas all fusion-negative tumors lacked clear cells. Our findings thus demonstrate that the CRTC1-MAML2 gene fusion is frequent in hidradenomas and is associated with clear cell variants of this tumor. Taken together, the present and previous observations indicate that the CRTC1-MAML2 fusion is etiologically linked to benign and low-grade malignant tumors originating from diverse exocrine glands rather than being linked to a separate tumor entity.
authors.affiliation: The Lundberg Laboratory for Cancer Research, Department of Pathology, Göteborg University, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: Marta
authors.initials: M
authors.lastname: Winnes
authors.forename: Lena
authors.initials: L
authors.lastname: Mölne
authors.forename: Mart
authors.initials: M
authors.lastname: Suurküla
authors.forename: Ywonne
authors.initials: Y
authors.lastname: Andrén
authors.forename: Fredrik
authors.initials: F
authors.lastname: Persson
authors.forename: Fredrik
authors.initials: F
authors.lastname: Enlund
authors.forename: Göran
authors.initials: G
authors.lastname: Stenman
mesh_terms: D006607:Adenoma, Sweat Gland / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013544:Sweat Gland Neoplasms / Q000235:genetics* / Q000378:metabolism*
chemical_list: C495418:MECT1-MAML2 fusion protein, human; D015514:Oncogene Proteins, Fusion