title: Characterization of genetic rearrangements in esophageal squamous carcinoma cell lines by a combination of M-FISH and array-CGH: further confirmation of some split genomic regions in primary tumors.
abstract: BACKGROUND
  Chromosomal and genomic aberrations are common features of human cancers. However, chromosomal numerical and structural aberrations, breakpoints and disrupted genes have yet to be identified in esophageal squamous cell carcinoma (ESCC).
  
  
  METHODS
  Using multiplex-fluorescence in situ hybridization (M-FISH) and oligo array-based comparative hybridization (array-CGH), we identified aberrations and breakpoints in six ESCC cell lines. Furthermore, we detected recurrent breakpoints in primary tumors by dual-color FISH.
  
  
  RESULTS
  M-FISH and array-CGH results revealed complex numerical and structural aberrations. Frequent gains occurred at 3q26.33-qter, 5p14.1-p11, 7pter-p12.3, 8q24.13-q24.21, 9q31.1-qter, 11p13-p11, 11q11-q13.4, 17q23.3-qter, 18pter-p11, 19 and 20q13.32-qter. Losses were frequent at 18q21.1-qter. Breakpoints that clustered within 1 or 2 Mb were identified, including 9p21.3, 11q13.3-q13.4, 15q25.3 and 3q28. By dual-color FISH, we observed that several recurrent breakpoint regions in cell lines were also present in ESCC tumors. In particular, breakpoints clustered at 11q13.3-q13.4 were identified in 43.3% (58/134) of ESCC tumors. Both 11q13.3-q13.4 splitting and amplification were significantly correlated with lymph node metastasis (LNM) (P = 0.004 and 0.022) and advanced stages (P = 0.004 and 0.039). Multivariate logistic regression analysis revealed that only 11q13.3-q13.4 splitting was an independent predictor for LNM (P = 0.026).
  
  
  CONCLUSIONS
  The combination of M-FISH and array-CGH helps produce more accurate karyotypes. Our data provide significant, detailed information for appropriate uses of these ESCC cell lines for cytogenetic and molecular biological studies. The aberrations and breakpoints detected in both the cell lines and primary tumors will contribute to identify affected genes involved in the development and progression of ESCC.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), Peking Union Medical College and Chinese Academy of Medical Science, 17 Panjiayuan Nanli, Chaoyang District, Beijing, 100021, China.
authors.forename: Jia-Jie
authors.initials: JJ
authors.lastname: Hao
authors.forename: Zhi-Zhou
authors.initials: ZZ
authors.lastname: Shi
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Zhao
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ting
authors.initials: T
authors.lastname: Gong
authors.forename: Chun-Xiang
authors.initials: CX
authors.lastname: Li
authors.forename: Ting
authors.initials: T
authors.lastname: Zhan
authors.forename: Yan
authors.initials: Y
authors.lastname: Cai
authors.forename: Jin-Tang
authors.initials: JT
authors.lastname: Dong
authors.forename: Song-Bin
authors.initials: SB
authors.lastname: Fu
authors.forename: Qi-Min
authors.initials: QM
authors.lastname: Zhan
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Wang
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations; D056905:Chromosome Breakpoints; D002877:Chromosomes, Human; D055028:Comparative Genomic Hybridization; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D005784:Gene Amplification; D017353:Gene Deletion; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D032681:Spectral Karyotyping; D014407:Tumor Cells, Cultured