title: Consistent and differential genetic aberrations between esophageal dysplasia and squamous cell carcinoma detected by array comparative genomic hybridization.
abstract: OBJECTIVE
  Our aim was to identify frequent genomic aberrations in both esophageal squamous cell carcinoma (ESCC) and esophageal dysplasia and to discover important copy number-driving genes and microRNAs (miRNA) in ESCC.
  
  
  METHODS
  We conducted array-based comparative genomic hybridization (array CGH) on 59 ESCC resection samples and 16 dysplasia biopsy samples. Expression of genes at 11q13.3 was analyzed by real-time PCR (RT-PCR) and immunohistochemistry (IHC). Integrated analysis was conducted to identify genes or miRNAs with copy number-expression correlations.
  
  
  RESULTS
  Array CGH identified 11 amplifications and eight homozygous deletions in ESCC. Integrated analysis of array CGH data with matched gene expression microarray data showed that 90 overexpressed genes and 24 underexpressed genes were consistent with DNA copy number changes, including 12 copy number-driving miRNAs. In esophageal dysplasia, six gains, four losses, 12 amplifications, and four homozygous deletions were detected. Amplifications of 7p11.2 and 11q13.2-11q13.3 (CCND1) and homozygous deletion at 9p21.3 (CDKN2A) were consistent genomic changes in both dysplasia and carcinoma. ANO1 at 11q13.3 was overexpressed at the mRNA and protein levels in tumors, and higher mRNA expression was correlated with the copy number increase. In particular, ANO1 expression was elevated in moderate dysplasia compared with normal esophageal epithelium. IHC revealed that ANO1 overexpression was positively correlated with lymph node metastasis and advanced clinical stage. Knockdown of ANO1 significantly inhibited the proliferation of KYSE30 and KYSE510 cells.
  
  
  CONCLUSIONS
  Copy number aberrations in both esophageal dysplasia and ESCC may be useful as potential biomarkers for early detection. In addition, ANO1 may be a candidate target gene in esophageal tumorigenesis.
authors.affiliation: Authors' Affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Zhi-Zhou
authors.initials: ZZ
authors.lastname: Shi
authors.forename: Li
authors.initials: L
authors.lastname: Shang
authors.forename: Yan-Yi
authors.initials: YY
authors.lastname: Jiang
authors.forename: Jia-Jie
authors.initials: JJ
authors.lastname: Hao
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Tong-Tong
authors.initials: TT
authors.lastname: Zhang
authors.forename: De-Chen
authors.initials: DC
authors.lastname: Lin
authors.forename: Shu-Guang
authors.initials: SG
authors.lastname: Liu
authors.forename: Bo-Shi
authors.initials: BS
authors.lastname: Wang
authors.forename: Ting
authors.initials: T
authors.lastname: Gong
authors.forename: Qi-Min
authors.initials: QM
authors.lastname: Zhan
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Wang
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics*; D045744:Cell Line, Tumor; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D004947:Esophagus / Q000378:metabolism* / Q000473:pathology*; D005784:Gene Amplification; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D011230:Precancerous Conditions / Q000235:genetics*