title: CpG island methylation profiling in human salivary gland adenoid cystic carcinoma.
abstract: BACKGROUND
  DNA methylation is a fundamental epigenetic event associated with physiologic and pathologic conditions, including cancer. Hypermethylation of CpG islands at active gene promoters leads to transcriptional repression, whereas hypomethylation is associated with gene overexpression. The aim of this study was to identify genes in adenoid cystic carcinoma (ACC) of salivary gland strongly deregulated by epigenetic CpG island methylation, to validate selected genes by conventional techniques, and to correlate the findings with clinicopathologic factors.
  
  
  METHODS
  The authors analyzed 16 matched normal and tumor tissues for aberrant DNA methylation using the methylated CpG island amplification and microarray method and the pyrosequencing technique.
  
  
  RESULTS
  Microarray analysis showed hypomethylation in 7 and hypermethylation in 32 CpG islands. Hypomethylation was identified in CpG islands near FBXO17, PHKG1, LOXL1, DOCK1, and PARVG. Hypermethylation was identified near genes encoding predominantly transcription factors (EN1, FOXE1, GBX2, FOXL1, TBX4, MEIS1, LBX2, NR2F2, POU3F3, IRX3, TFAP2C, NKX2-4, PITX1, NKX2-5), and 13 genes with different functions (MT1H, EPHX3, AQPEP, BCL2L11, SLC35D3, S1PR5, PNLIPRP1, CLIC6, RASAL, XRN2, GSTM5, FNDC1, INSRR). Four CpG islands by EN1, FOXE1, TBX4, and PITX1 were validated by pyrosequencing.
  
  
  CONCLUSIONS
  The highly methylated genes in tumor versus normal tissue are linked to developmental, apoptotic, and other fundamental cellular pathways, suggesting that down-regulation of these genes is associated with ACC development and progression. With EN1 hypermethylation showing potential as a possible biomarker for ACC in salivary gland, the biological and therapeutic implications of these findings require further preclinical investigations.
authors.affiliation: Department of Pathology and Cancer Institute, The University of Mississippi Medical Center, Jackson, Mississippi, USA. abell2@umc.edu
authors.forename: Achim
authors.initials: A
authors.lastname: Bell
authors.forename: Diana
authors.initials: D
authors.lastname: Bell
authors.forename: Randal S
authors.initials: RS
authors.lastname: Weber
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012468:Salivary Gland Neoplasms / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics
chemical_list: D014157:Transcription Factors