title: Whole-Exome Sequencing of Salivary Gland Mucoepidermoid Carcinoma.
abstract: OBJECTIVE
  Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. To explore the genetic origins of MEC, we performed systematic genomic analyses of these tumors.
  
  
  METHODS
  Whole-exome sequencing and gene copy-number analyses were performed for 18 primary cancers with matched normal tissue. FISH was used to determine the presence or absence of the MECT1-MAML2 translocation in 17 tumors.
  
  
  RESULTS
  TP53 was the most commonly mutated gene in MEC (28%), and mutations were found only in intermediate- and high-grade tumors. Tumors with TP53 mutations had more mutations overall than tumors without TP53 mutations (P = 0.006). POU6F2 was the second most frequently mutated gene, found in three low-grade MECs with the same in-frame deletion. Somatic alterations in IRAK1, MAP3K9, ITGAL, ERBB4, OTOGL, KMT2C, and OBSCN were identified in at least two of the 18 tumors sequenced. FISH analysis confirmed the presence of the MECT1-MAML2 translocation in 15 of 17 tumors (88%).
  
  
  CONCLUSIONS
  Through these integrated genomic analyses, MECT1-MAML2 translocation and somatic TP53 and POU6F2 mutations appear to be the main drivers of MEC. Clin Cancer Res; 23(1); 283-8. ©2016 AACR.
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Hyunseok
authors.initials: H
authors.lastname: Kang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Marietta
authors.initials: M
authors.lastname: Tan
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Bishop
authors.affiliation: Personal Genome Diagnostics, Baltimore, Maryland.
authors.forename: Siân
authors.initials: S
authors.lastname: Jones
authors.affiliation: Personal Genome Diagnostics, Baltimore, Maryland.
authors.forename: Mark
authors.initials: M
authors.lastname: Sausen
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Patrick K
authors.initials: PK
authors.lastname: Ha
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland. nishant.agrawal@uchicago.edu.|Department of Surgery, Section of Otolaryngology-Head and Neck Surgery, University of Chicago, Chicago, Illinois.
authors.forename: Nishant
authors.initials: N
authors.lastname: Agrawal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D018277:Carcinoma, Mucoepidermoid / Q000235:genetics* / Q000473:pathology; D056915:DNA Copy Number Variations; D059472:Exome; D005260:Female; D023281:Genomics / Q000379:methods; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic; D000073359:Exome Sequencing
chemical_list: D014408:Biomarkers, Tumor; C495418:MECT1-MAML2 fusion protein, human; D015514:Oncogene Proteins, Fusion