title: Mutational landscape of lacrimal gland carcinomas and implications for treatment.
abstract: Lacrimal gland carcinomas are rare. Identification of molecular abnormalities underlying lacrimal gland carcinogenesis is critical to the development of new targeted therapies for lacrimal gland carcinomas. The purpose of our study was to look for mutations that can be targeted as new treatments for lacrimal gland carcinomas.
  
  
  
  Genomic DNA from patients with lacrimal gland epithelial neoplasms was analyzed. The Sequenom matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass ARRAY platform was used to profile 168 common oncogenic point mutations in 40 genes. Mutation frequency was assessed overall and by histologic diagnosis. These genetic mutations were then correlated with clinical outcomes in the patients.
  
  
  
  The study included 14 men and 10 women with a median age of 45 years (range, 17-75 years). The histologic diagnoses were as follows: adenoid cystic carcinoma (n = 16), low-grade carcinoma ex pleomorphic adenoma (n = 2), high-grade carcinoma ex pleomorphic adenoma (n = 2), squamous carcinoma (n = 1), and pleomorphic adenoma (n = 3). Analysis revealed 18 oncogenic mutations in 13 patients: KRAS mutations in 10 patients (46%), NRAS mutations in 2 patients (8%), MET mutations in 3 patients (13%), PIK3CA mutation in 1 patient (4%), and BRAF mutation in no patients. About half of the patients with adenoid cystic carcinoma had oncogenic mutations (7 of 16; 44%). Of the 16 patients with adenoid cystic carcinoma, 5 had KRAS mutations, 1 had MET mutations, and 1 had an NRAS mutation.
  
  
  
  KRAS, NRAS, and MET mutations are frequent in epithelial neoplasms of the lacrimal gland, with the highest rate of mutations found in adenoid cystic carcinoma. Therapies targeting these genes may be effective treatments for lacrimal gland carcinomas. © 2015 Wiley Periodicals, Head Neck 38: E-E, 2016.
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Diana
authors.initials: D
authors.lastname: Bell
authors.affiliation: Orbital Oncology and Ophthalmic Plastic Surgery Program, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Sniegowski
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Khalida
authors.initials: K
authors.lastname: Wani
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Victor
authors.initials: V
authors.lastname: Prieto
authors.affiliation: Orbital Oncology and Ophthalmic Plastic Surgery Program, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Bita
authors.initials: B
authors.lastname: Esmaeli
mesh_terms: D008949:Adenoma, Pleomorphic / Q000235:genetics / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D005134:Eye Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D007765:Lacrimal Apparatus / Q000473:pathology; D007766:Lacrimal Apparatus Diseases / Q000235:genetics* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D055815:Young Adult
chemical_list: C117307:KRAS protein, human; D008565:Membrane Proteins; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Sequenom; lacrimal gland carcinomas; molecular abnormalities; mutations; targeted therapies