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. 2021 May;478(5):933-941.
doi: 10.1007/s00428-020-02971-w. Epub 2020 Nov 25.

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  10
Affiliations

ALK alterations in salivary gland carcinomas

Hanna Majewska et al. Virchows Arch. 2021 May.

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; FISH; Immunohistochemistry; Intraductal carcinoma; Next generation sequencing; Salivary gland carcinoma.

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Conflict of interest statement

Prof Rafał Dziadziuszko: Advisory board role for Pfizer, Novartis, Roche, Takeda, Merck, Seattle Genetics, and Foundation Medicine. Travel costs from Roche and AstraZeneca. Dr. Johannes Heuckmann is a full time employee of NEO New Oncology GmbH. Prof Jacek Jassem: Advisory board role for Boehringer, Astra Zeneca, BMS, and Merck. Other authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Intraductal carcinoma. a The unencapsulated tumor composed of variably sized cysts and nests with mainly intraductal proliferations The neoplastic nests contain epithelioid cells with abundant eosinophilic cytoplasm and regular oval and round nuclei with conspicuous nucleoli (H&E × 20). b The cysts contained micropapillary structures, solid areas with irregular fenestrations or cribriform areas(H&E × 20). c–d The neoplastic nests contain epithelioid cells with abundant eosinophilic cytoplasm and regular oval and round nuclei with conspicuous nucleoli (c H&E × 200; d H&E × 100). e Focal mucinous differentiation with PAS-positive vacuoles in the cytoplasm (H&E × 200). f Immunohistochemical staining showed strong membranous expression of ALK in 100% of cells (H&E × 200). g Fluorescence in situ hybridization with ALK Dual Color Break Apart FISH Probe. Nuclei with split red and green signals indicate ALK break (yellow arrows). Chromosome 2 with normal gene shows yellow signal (overlapping green and red and white arrows)
Fig. 2
Fig. 2
Identification of the novel MYO18A (Exon1-40)-ALK (exon 20-29) gene fusion detected in intraductal carcinoma. a Breakpoint spanning reads in exon 20 of ALK. The spanning reads have both aligned (grey) and misaligned bases (colored). The misaligned bases correspond to a region of MYO18A. b Encompassing reads in MYO18A (red). The corresponding mate of the reads of MYO18A align to a region in ALK. c Schematic representation of the MYO18A-ALK gene fusion
See this image and copyright information in PMC

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