title: CRTC1-MAML2 and CRTC3-MAML2 fusions were not detected in metaplastic Warthin tumor and metaplastic pleomorphic adenoma of salivary glands.
abstract: The recurrent translocations t(11;19) and t(11;15) resulting in CRTC1-MAML2 or CRTC3-MAML2 fusion oncogenes, respectively, are identified in a large proportion of mucoepidermoid carcinomas (MECs) of the salivary gland and have impact on prognosis. However, there are conflicting data on the specificity of this translocation, in particular, on its putative occurrence in Warthin tumor (WT) of the parotid gland as reported in few previous cases. It was speculated that extensive squamous metaplasia could explain the presence of t(11;19) translocation in a subset of WTs. We evaluated 76 salivary gland tumors, including 16 cases of metaplastic WT and 8 cases of pleomorphic adenoma (PA) with squamous and/or mucinous metaplasia, extensive enough morphologically to mimic MEC. Detection of CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts and MAML2 gene break was performed using nested reverse transcription-polymerase chain reaction and fluorescence in situ hybridization (FISH), respectively. None of 16 analyzed metaplastic WTs showed positivity for fusion transcripts CRTC1-MAML2 or CRTC3-MAML2, and none showed rearrangement of the MAML2 gene by FISH. Similarly, we did not detect these transcripts or break of MAML2 gene in any case of PA with extensive squamous/mucinous metaplasia. For comparison, 40 cases of low-grade MEC were also evaluated. CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts were detected in 17 and 5 cases, respectively. The FISH method using break-apart probe demonstrated the MAML2 gene rearrangement in 25 cases of low-grade MEC. In contrast to low-grade MEC, neither metaplastic WTs nor metaplastic PAs harbored translocations t(11;19) and anticipated t(11;15) resulting in CRTC1-MAML2 and CRTC3-MAML2 fusion transcripts, respectively, and/or MAML2 gene rearrangement.
authors.affiliation: *Department of Pathology, Faculty of Medicine in Plzen, Charles University in Prague †Bioptic Laboratory Ltd ‡Bioptic Laboratory Ltd, Molecular Pathology Laboratory #Department of Maxillofacial Surgery, Clinic of Dentistry, Faculty of Medicine in Plzen, Plzen, Czech Republic §Department of Anatomical Pathology, University of Calgary and Foothills Medical Center, Calgary, Canada ∥Pathology Research Group, N.N. Alexandrov's Research Center of Oncology and Medical Radiology, Minsk, Republic of Belarus ¶Department of Pathology, Medical University of Gdansk, Gdansk, Poland.
authors.forename: Alena
authors.initials: A
authors.lastname: Skálová
authors.forename: Tomas
authors.initials: T
authors.lastname: Vanecek
authors.forename: Roderick H W
authors.initials: RH
authors.lastname: Simpson
authors.forename: Marina A
authors.initials: MA
authors.lastname: Vazmitsel
authors.forename: Hanna
authors.initials: H
authors.lastname: Majewska
authors.forename: Petr
authors.initials: P
authors.lastname: Mukensnabl
authors.forename: Lukas
authors.initials: L
authors.lastname: Hauer
authors.forename: Pavel
authors.initials: P
authors.lastname: Andrle
authors.forename: Lubor
authors.initials: L
authors.lastname: Hosticka
authors.forename: Petr
authors.initials: P
authors.lastname: Grossmann
authors.forename: Michal
authors.initials: M
authors.lastname: Michal
mesh_terms: D000235:Adenolymphoma / Q000235:genetics* / Q000473:pathology; D008949:Adenoma, Pleomorphic / Q000235:genetics* / Q000473:pathology; D001706:Biopsy; D004268:DNA-Binding Proteins / Q000235:genetics*; D050939:Gene Fusion; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008679:Metaplasia; D060787:Neoplasm Grading; D009687:Nuclear Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C500984:CRTC1 protein, human; C495791:CRTC3 protein, human; D004268:DNA-Binding Proteins; C471297:MAML2 protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors