ALK alterations in salivary gland carcinomas
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ORIGINAL ARTICLE
ALK alterations in salivary gland carcinomas Hanna Majewska 1 & Adam Gorczyński 1 & Piotr Czapiewski 1 & Roopika Menon 2 & Judith Mueller 2 & Sotirios Lakis 2 & Johannes M. Heuckmann 2 & Jan Laco 3 & Ruta Gupta 4 & Simon Andreasen 5 & Dominik Stodulski 6 & Mariola Iliszko 7 & Rafał Dziadziuszko 8 & Jacek Jassem 8 & Lukas C. Heukamp 9 & Wojciech Biernat 1 Received: 2 August 2020 / Revised: 25 October 2020 / Accepted: 15 November 2020 # The Author(s) 2020
Abstract Salivary gland carcinomas represent a heterogeneous group of poorly characterized head and neck tumors. The purpose of this study was to evaluate ALK gene and protein aberrations in a large, well-characterized cohort of these tumors. A total of 182 salivary gland carcinomas were tested for anaplastic lymphoma kinase (ALK) positivity by immunohistochemistry (IHC) using the cut-off of 10% positive cells. ALK positive tumors were subjected to FISH analysis and followed by hybrid capture–based next generation sequencing (NGS). Of the 182 tumors, 8 were ALK positive by IHC. Further analysis using hybrid capture NGS analysis revealed a novel MYO18A (Exon1-40)-ALK (exon 20-29) gene fusion in one case of intraductal carcinoma. Additional genomic analyses resulted in the detection of inactivating mutations in BRAF and TP53, as well as amplifications of ERBB2 and ALK. ALK rearrangements are a rare entity in salivary gland carcinomas. We identified a potentially targetable novel ALK fusion in an intraductal carcinoma of minor salivary glands. Keywords Anaplastic lymphoma kinase . Salivary gland carcinoma . Intraductal carcinoma . FISH . Immunohistochemistry . Next generation sequencing
Introduction Salivary gland tumors comprise a heterogeneous group of benign and malignant neoplasms, accounting for approximately 6% of all head and neck cancers. Salivary gland carcinomas (SGCs) are rare and characterized by extensive morphological diversity and variable clinical behavior [1]. Molecular genetic studies have recently revealed that gene rearrangements play a significant role in the molecular pathogenesis of SGCs [1]. These translocations are associated with
specific histological subtypes or with particular morphological patterns. For instance, the translocations t(11;19) and t(11;15), resulting in CRTC1-MAML2 or CRTC3-MAML2 fusion oncogenes, respectively, are relatively common in mucoepidermoid carcinomas (MECs) originating in diverse anatomical locations [2–4]. ETV6-NTRK3 and ETV6-RET translocation was found to be specific for secretory carcinoma (a.k.a. mammary analogue secretory carcinoma, MASC) and has not been documented in any other salivary gland tumor [5, 6]. Around 80–90% of adenoid cystic carcinomas (AdCC)
Dr. Sotirios Lakis is no longer an employee of New Oncology * Wojciech Biernat [email protected]
5
Department of Otorhinolaryngology and Maxillofacial Surgery, Køge University Hospital, Køge, Denmark
6
Department of Otolaryngology, Medical University of Gdańsk, Gdańsk, Poland
1
Department of Pathomorphology, Medical University o
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