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Background  Salivary duct carcinoma (SDC) is a highly aggressive subtype of salivary gland cancers and there is no established standard therapy for this disease. Thus, development of molecular markers for SDC will be important to guide the diagnosis and therapy of this aggressive tumor.    Methods  We performed next-generation sequencing using the Ion Torrent AmpliSeq cancer panel, which explores the mutational status of hotspot regions in 50 cancer-associated genes, and we analyzed copy number variations (CNVs) of 21 genes by NanoString nCounter for 37 patients with SDC. Fluorescent in situ hybridization was also conducted to confirm  ERBB2  gene amplification. Clinical records and tumor histopathology of the patients were retrospectively reviewed.    Results  Genetic alterations were detected in 29 of 37 (78.3%) tumors, including mutations in  PIK3CA  ( N  = 9, 24.3%),  ERBB2  ( N  = 4, 10.8%), and  EGFR  ( N  = 4, 10.8%). To our knowledge, this is the first time that  ERBB2  mutations have been reported in this tumor type. Both  PIK3CA  and  ERBB2  mutation status were associated with poor overall survival, but without statistical significance.  ERBB2  amplification was strong and common in SDC and almost all cases also exhibited  EGFR  and  ERBB3  amplifications.    Conclusions  This study reports the largest and most comprehensive analysis of DNA aberrations in SDC. Our results show that  PIK3CA  and/or  ERBB2  alterations in the development of SDC might be a useful diagnostic tool and could serve as a potential therapeutic target.

High-throughput profiling identifies clinically actionable mutations in salivary duct carcinoma