title: NUT rearrangement is uncommon in human thymic epithelial tumors.
abstract: BACKGROUND
  Thymic carcinomas represent the most aggressive histotype of thymic epithelial tumors (TETs). The 2004 World Health Organization classification has assigned a subgroup of thymic carcinomas as t(15;19) carcinomas based on the presence of t(15;19), a translocation found in poorly differentiated and highly aggressive NUT midline carcinomas. These tumors are characterized byrearrangement of the NUT (nuclear protein in testis) gene on chromosome 15q14, which in most cases fuses to the bromodomain containing 4 (BRD4) gene on chromosome 19 p13.1 through reciprocal t(15;19) translocation, resulting in constitutive BRD4-NUTfusion protein expression. To our knowledge, NUT translocation has been reported only in four thymic carcinomas. Due to the rarity of TETs, the prevalence of NUT rearrangement in TETs has however never been systematically explored.
  
  
  METHODS
  Formalin-fixed paraffin-embedded samples of histologically confirmed TETs were evaluated for NUT expression and rearrangement by immunohistochemistry and fluorescence in situ hybridization, respectively.
  
  
  RESULTS
  A series of 148 TETs (37 carcinomas and 111 thymomas) were examined for NUT expression and rearrangement. Only one thymic carcinoma (2.7% of thymic carcinomas or 0.68% of TETs) was found positive for NUT expression and rearrangement.
  
  
  CONCLUSIONS
  Rearrangement of NUT is infrequent in TETs. We propose that caution should be taken to distinguish t(15;19) thymic carcinoma from other mediastinal carcinomas, as NUT midline carcinomas are often associated with dreadful prognosis or overt lethality.
authors.affiliation: Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Petrini
authors.initials: P
authors.lastname: Petrini
authors.forename: Christopher A
authors.initials: CA
authors.lastname: French
authors.forename: Arun
authors.initials: A
authors.lastname: Rajan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cameron
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Zucali
authors.forename: Jianwu
authors.initials: J
authors.lastname: Xie
authors.forename: Yisong
authors.initials: Y
authors.lastname: Wang
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giaccone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics*; D015513:Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics; D013953:Thymus Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D014157:Transcription Factors; D000092468:Bromodomain Containing Proteins
chemical_list: D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C109106:BRD3 protein, human; D000092468:Bromodomain Containing Proteins; C000630260:NUTM1 protein, human