title: Molecular cytogenetic analysis of head and neck squamous cell carcinoma: By comparative genomic hybridization, spectral karyotyping, and expression array analysis.
abstract: BACKGROUND
  A combination of molecular cytogenetic and expression array analysis has been performed on head and neck squamous cell carcinoma (HNSCC) of the oral cavity and supraglottis. These studies were performed to identify consensus regions of chromosomal imbalance and structural rearrangement to determine whether genes located in these genomic regions are subject to alterations in gene expression. Such combinatorial studies may help to identify recurrent patterns of altered gene expression in the context of specific chromosomal changes.
  
  
  METHODS
  Comparative genomic hybridization (CGH) was used to identify net genomic imbalances and spectral karyotyping (SKY) to visualize the numerical and structural chromosomal changes in metaphase preparations. Expression microarray analysis of HNSCC cell lines and primary tongue tumors was also performed to identify genes that were commonly overexpressed or underexpressed compared with adjacent normal tissue.
  
  
  RESULTS
  CGH detected gains at 3q (64%), 8q (45%) and 6q22-qter (45%) and losses at 18q22-qter (27%). SKY analysis of seven cell lines identified frequent structural rearrangement of the following chromosomal regions: 3q, 5p13-q11.2, 5q32-q34, 7p12-q11.2, 8p12-q12, 9p, 10p, 13p13-q12, 14q11.1-q11.2, 15p13-q11.2, 16p11.1-q11.1, 18q22-q23, and 22p13-q11.2. Consistent deregulation of interleukin 8, integrin alpha-6, c-MYC, epithelial discoidin domain receptor 1, and sterol regulatory element binding protein were apparent by expression analysis. Interestingly, some of these genes map to regions of genomic imbalance and chromosomal rearrangement as determined by our molecular cytogenetic analysis.
  
  
  CONCLUSIONS
  In this small study, a combinatorial analysis using SKY, CGH, and microarray provides a model linking the changes in gene expression to changes in chromosomal dosage and structure. This approach has identified a subset of genetic changes that provide new opportunities for investigating the genetic basis of tumorigenesis in HNSCC.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, The University of Toronto and The University Health Network, Toronto, Ontario, Canada. jeremy.squire@utoronto.ca
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Squire
authors.forename: Jane
authors.initials: J
authors.lastname: Bayani
authors.forename: Catherine
authors.initials: C
authors.lastname: Luk
authors.forename: Lianne
authors.initials: L
authors.lastname: Unwin
authors.forename: Jason
authors.initials: J
authors.lastname: Tokunaga
authors.forename: Christina
authors.initials: C
authors.lastname: MacMillan
authors.forename: Jonathan
authors.initials: J
authors.lastname: Irish
authors.forename: Dale
authors.initials: D
authors.lastname: Brown
authors.forename: Patrick
authors.initials: P
authors.lastname: Gullane
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kamel-Reid
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D020732:Cytogenetic Analysis / Q000379:methods*; D004273:DNA, Neoplasm / Q000235:genetics; D015536:Down-Regulation; D020869:Gene Expression Profiling; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D007621:Karyotyping / Q000379:methods; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D012334:RNA, Neoplasm / Q000235:genetics; D014062:Tongue Neoplasms / Q000235:genetics; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D004273:DNA, Neoplasm; D012334:RNA, Neoplasm