Immunohistochemical, FISH and Genomic Profiling Study of Salivary Gland Carcinomas Reveals a Novel MYO18A-ALK Gene Rearrangement

Abstract

Background: 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, wellcharacterized cohort of these tumors. Materials and methods: 182 salivary gland carcinomas were tested for ALK positivity by immunohistochemistry 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). Results: Of the 182 tumors, 8 were ALK positive. Further analysis showed ALK amplification in one case of intraductal carcinoma/low grade cribriform cystadenocarcinoma (LGCCC). Hybrid capture NGS analysis revealed a novel MYO18A (Exon1-40)-ALK (exon 20-29) gene fusion. Additional genomic analyses resulted in the detection of inactivating mutations in BRAF and TP53, as well as amplifications of ERBB2. Conclusion: We identified a potentially targetable novel ALK fusion in an intraductal carcinoma/LGCCCC of minor salivary glands.