ALK alterations in salivary gland carcinomas

Hanna Majewska,Rafał Dziadziuszko,Mariola Iliszko,Adam Gorczyński,Sotirios Lakis,Lukas C Heukamp,Johannes M Heuckmann,Simon Andreasen,Roopika Menon,Wojciech Biernat,Ruta Gupta,Jacek Jassem,Piotr Czapiewski,Judith Mueller,Dominik Stodulski,Jan Laco

doi:10.1007/s00428-020-02971-w

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.

Highlights

Salivary gland tumors comprise a heterogeneous group of benign and malignant neoplasms, accounting for approximately 6% of all head and neck cancers
Out of 182 Salivary gland carcinomas (SGCs) we screened by IHC, only eight samples expressed anaplastic lymphoma kinase (ALK) in more than 10% of tumor cells with moderate to strong staining intensity
fluorescence in situ hybridization (FISH) and hybrid capture–based generation sequencing analysis performed in these tumors identified one case with a low-level amplification in the ALK gene (CAMSG with 30% nuclear positivity)

Summary

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. 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].

Objectives

Methods

Results

Conclusion