title: Progressive genetic alterations of adenoid cystic carcinoma with high-grade transformation.
abstract: BACKGROUND
  Although genome-wide imbalances have been characterized in conventional adenoid cystic carcinoma, other than p53 mutational status, the molecular profile of adenoid cystic carcinoma with high-grade transformation has not been explored.
  
  
  OBJECTIVE
  To evaluate progressive genetic alterations in adenoid cystic carcinoma with high-grade transformation using array comparative genomic hybridization.
  
  
  METHODS
  Five adenoid cystic carcinomas with high-grade transformation (4 primary tumors and 1 paired metastasis) were selected and characterized at the DNA level by array comparative genomic hybridization on formalin-fixed paraffin-embedded tissue. Select alterations were validated by fluorescence in situ hybridization.
  
  
  RESULTS
  Chromosomal gains were mostly confined to the areas of high-grade transformation while losses were seen only in the conventional areas. Chromosomal regions with significant gains included 8q24, 17q11.2-q12, 17q23, and 15q11-13. Regions that showed the significant losses included 9q34, 4p16, 1p36.1, and 11q22. Fluorescence in situ hybridization analysis demonstrated increases in C-MYC (8q24.12-q24.13) and a low level increases in ERBB2 ( formerly HER2/neu ) (17q11.2-q12) in cases showing gains by array comparative genomic hybridization in these regions. However, no tumor showed HER2/ neu immunopositivity.
  
  
  CONCLUSIONS
  High-grade transformation in adenoid cystic carcinoma is a complex process that is reflected by several chromosomal alterations. Our findings implicate C-MYC amplification in this progression, although the role of HER2/neu is still unclear. Other candidate oncogenes, particularly on chromosome 17q23, warrant investigation in this rare tumor.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pittsburgh, 200 Lothrop St., Pittsburgh, PA 15213, USA. seethalarr@upmc.edu
authors.forename: Raja R
authors.initials: RR
authors.lastname: Seethala
authors.forename: Kathleen
authors.initials: K
authors.lastname: Cieply
authors.forename: E Leon
authors.initials: EL
authors.lastname: Barnes
authors.forename: Sanja
authors.initials: S
authors.lastname: Dacic
mesh_terms: D000328:Adult; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D018734:Genes, erbB-2; D016259:Genes, myc; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology