title: High-throughput profiling identifies clinically actionable mutations in salivary duct carcinoma.
abstract: 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.
authors.forename: Bo Mi
authors.initials: BM
authors.lastname: Ku
authors.forename: Hyun Ae
authors.initials: HA
authors.lastname: Jung
authors.forename: Jong-Mu
authors.initials: JM
authors.lastname: Sun
authors.forename: Young Hyeh
authors.initials: YH
authors.lastname: Ko
authors.forename: Han-Sin
authors.initials: HS
authors.lastname: Jeong
authors.forename: Young-Ik
authors.initials: YI
authors.lastname: Son
authors.forename: Chung-Hwan
authors.initials: CH
authors.lastname: Baek
authors.forename: Keunchil
authors.initials: K
authors.lastname: Park
authors.forename: Myung-Ju
authors.initials: MJ
authors.lastname: Ahn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018987:Salivary Ducts / Q000473:pathology*; D012468:Salivary Gland Neoplasms / Q000235:genetics*