title: Detection of novel actionable genetic changes in salivary duct carcinoma helps direct patient treatment.
abstract: OBJECTIVE
  Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland cancers for which cytotoxic chemotherapy has limited efficacy. We investigated whether genotyping analysis could detect novel tumor-specific mutations that would help direct SDC patient treatment using targeted agents.
  
  
  METHODS
  We genotyped 27 SDC archival specimens from patients followed at Massachusetts General Hospital and Massachusetts Eye and Ear Infirmary (Boston, MA) between 2000 and 2011. These included the tumors of 8 patients who were tested prospectively. Targeted mutational analysis of 13 clinically relevant cancer genes was conducted using SNaPshot multiplexed genotyping. FISH was conducted to detect HER2 gene amplification. Patient medical records and tumor histopathologic features were retrospectively reviewed.
  
  
  RESULTS
  Mutually exclusive genetic aberrations were detected in 15 of 27 (56%) tumors, including 2 (7%) mutations in BRAF, 5 (19%) mutations in PIK3CA, and 8 (30%) cases of HER2 gene amplification. To our knowledge, this is the first time that BRAF and PIK3CA mutations have been reported in this tumor type. Prospective clinical testing of 8 patients with SDC identified actionable genetic alterations in 6 tumors and influenced therapeutic decisions for all 6 patients.
  
  
  CONCLUSIONS
  SNaPshot molecular profiling identified novel genetic changes in SDCs, expanded the therapeutic options for patients with this rare tumor, and is changing SDC management at our institution. These findings highlight the importance of using broad-based genetic profiling to expedite the identification of effective-targeted therapies for patients with rare malignancies.
authors.affiliation: Departments of Pathology and Medicine, Massachusetts General Hospital; Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Nardi
authors.forename: Peter M
authors.initials: PM
authors.lastname: Sadow
authors.forename: Dejan
authors.initials: D
authors.lastname: Juric
authors.forename: Dave
authors.initials: D
authors.lastname: Zhao
authors.forename: Arjola K
authors.initials: AK
authors.lastname: Cosper
authors.forename: Kristin
authors.initials: K
authors.lastname: Bergethon
authors.forename: Vanessa L
authors.initials: VL
authors.lastname: Scialabba
authors.forename: Julie M
authors.initials: JM
authors.lastname: Batten
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Borger
authors.forename: Anthony John
authors.initials: AJ
authors.lastname: Iafrate
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Heist
authors.forename: Donald P
authors.initials: DP
authors.lastname: Lawrence
authors.forename: Keith T
authors.initials: KT
authors.lastname: Flaherty
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Bendell
authors.forename: Daniel
authors.initials: D
authors.lastname: Deschler
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Wirth
authors.forename: Dora
authors.initials: D
authors.lastname: Dias-Santagata
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D044584:Carcinoma, Ductal / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D005260:Female; D005784:Gene Amplification; D020869:Gene Expression Profiling; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D012468:Salivary Gland Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D058534:Class I Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf; D018719:Erb-b2 Receptor Tyrosine Kinases; C484760:PIK3CA protein, human