title: Profiling of 149 Salivary Duct Carcinomas, Carcinoma Ex Pleomorphic Adenomas, and Adenocarcinomas, Not Otherwise Specified Reveals Actionable Genomic Alterations.
abstract: OBJECTIVE
  We sought to identify genomic alterations (GA) in salivary gland adenocarcinomas, not otherwise specified (NOS), salivary duct carcinomas (SDC), carcinoma ex pleomorphic adenoma (ca ex PA), and salivary carcinoma, NOS.
  
  
  METHODS
  DNA was extracted from 149 tumors. Comprehensive genomic profiling (CGP) was performed on hybridization-captured adaptor ligation-based libraries of 182 or 315 cancer-related genes plus introns from 14 or 28 genes frequently rearranged for cancer and evaluated for all classes of GAs.
  
  
  RESULTS
  A total of 590 GAs were found in 157 unique genes (mean 3.9/tumor). GAs in the PI3K/AKT/mTOR pathway were more common in SDC (53.6%) than other histologies (P = 0.019) Cyclin-dependent kinase GAs varied among all histotypes: adenocarcinoma, NOS (34.6%); SDC (12.2%); ca ex PA (16.7%); carcinoma, NOS (31.2%; P = 0.043). RAS GAs were observed: adenocarcinoma, NOS (17.3%); SDC (26.8%); ca ex PA (4.2%); and carcinoma, NOS (9.4%; P = 0.054). ERBB2 GAs, including amplifications and mutations, were common: adenocarcinoma, NOS (13.5%); SDC (26.8%); ca ex PA (29.2%); carcinoma, NOS (18.8; P = 0.249). Other notable GAs include TP53 in >45% of each histotype; NOTCH1: adenocarcinoma, NOS (7.7%), ca ex PA (8.3%), carcinoma, NOS (21.6%); NF1: adenocarcinoma, NOS (9.6%), SDC (17.1%), carcinoma, NOS (18.8%). RET fusions were identified in one adenocarcinoma, NOS (CCDC6-RET) and two SDCs (NCOA4-RET). Clinical responses were observed in patients treated with anti-HER2 and anti-RET-targeted therapies.
  
  
  CONCLUSIONS
  CGP of salivary adenocarcinoma, NOS, SDCs, ca ex PA, and carcinoma, NOS revealed diverse GAs that may lead to novel treatment options. Clin Cancer Res; 22(24); 6061-8. ©2016 AACR.
authors.affiliation: Foundation Medicine, Inc, Cambridge, Massachusetts.|Zhejiang Cancer Hospital, Hangzhou, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Moffitt Cancer Center, University of South Florida, Tampa, Florida.
authors.forename: Jeffery S
authors.initials: JS
authors.lastname: Russell
authors.affiliation: Division of Medical Oncology, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Jessica D
authors.initials: JD
authors.lastname: McDermott
authors.affiliation: Foundation Medicine, Inc, Cambridge, Massachusetts.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Elvin
authors.affiliation: Foundation Medicine, Inc, Cambridge, Massachusetts.
authors.forename: Depinder
authors.initials: D
authors.lastname: Khaira
authors.affiliation: Foundation Medicine, Inc, Cambridge, Massachusetts.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Johnson
authors.affiliation: Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Jennings
authors.affiliation: Foundation Medicine, Inc, Cambridge, Massachusetts.
authors.forename: Siraj M
authors.initials: SM
authors.lastname: Ali
authors.affiliation: Foundation Medicine, Inc, Cambridge, Massachusetts.
authors.forename: Molly
authors.initials: M
authors.lastname: Murray
authors.affiliation: Department of Pathology, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Carrie
authors.initials: C
authors.lastname: Marshall
authors.affiliation: Centra Hematology Oncology Clinic, Alan B. Pearson Regional Cancer Center, Lynchburg, Virginia.
authors.forename: Dwight S
authors.initials: DS
authors.lastname: Oldham
authors.affiliation: Centra Hematology Oncology Clinic, Alan B. Pearson Regional Cancer Center, Lynchburg, Virginia.
authors.forename: Donna
authors.initials: D
authors.lastname: Washburn
authors.affiliation: Division of Hematology Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Wong
authors.affiliation: Foundation Medicine, Inc, Cambridge, Massachusetts.
authors.forename: Juliann
authors.initials: J
authors.lastname: Chmielecki
authors.affiliation: Foundation Medicine, Inc, Cambridge, Massachusetts.
authors.forename: Roman
authors.initials: R
authors.lastname: Yelensky
authors.affiliation: Foundation Medicine, Inc, Cambridge, Massachusetts.
authors.forename: Doron
authors.initials: D
authors.lastname: Lipson
authors.affiliation: Foundation Medicine, Inc, Cambridge, Massachusetts.
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.affiliation: Foundation Medicine, Inc, Cambridge, Massachusetts.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Stephens
authors.affiliation: Department of Pathology, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Hilary S
authors.initials: HS
authors.lastname: Serracino
authors.affiliation: Foundation Medicine, Inc, Cambridge, Massachusetts. daniel.bowles@ucdenver.edu jross@foundationmedicine.com.|Department of Pathology, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ross
authors.affiliation: Division of Medical Oncology, University of Colorado School of Medicine, Aurora, Colorado. daniel.bowles@ucdenver.edu jross@foundationmedicine.com.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Bowles
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D008949:Adenoma, Pleomorphic / Q000235:genetics*; D044584:Carcinoma, Ductal / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics*; D023281:Genomics / Q000379:methods; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D018987:Salivary Ducts / Q000378:metabolism; D012468:Salivary Gland Neoplasms / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D018719:Erb-b2 Receptor Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases