title: HER2, TOP2A, CCND1, EGFR and C-MYC oncogene amplification in colorectal cancer.
abstract: OBJECTIVE
  Recent studies had suggested substantial molecular differences between tumours from different ethnic groups. In this study, the molecular differences between the incidences of colorectal carcinoma in Saudi and Swiss populations are investigated.
  
  
  METHODS
  518 cases of colon cancer tumours (114 from Saudi Arabia and 404 from Switzerland) were analysed in a tissue microarray format. Fluorescence in situ hybridisation (FISH) was used to estimate frequencies of copy number changes of known oncogenes, including HER2, TOPO2A, CCND1, EGFR and C-MYC.
  
  
  RESULTS
  Using FISH, amplifications were mostly low level (gene-to-centromere ratio 2 to 4), which is in contrast with other tumour types with more frequent gene amplifications. The amplifications were particularly frequent for MYC (Saudi 9% and Swiss 14.2%) but unrelated to clinical outcome and pathological information. Remarkably, there were four tumours exhibiting classic high-level gene amplification for HER2 (Swiss 1.3%), a pattern often accompanied by response to trastuzumab (Herceptin) in breast cancer. Occasional high-level amplifications were also observed for CCND1 (Saudi 1/106, 0.9%; Swiss 2/373, 0.5%) and EGFR (Swiss 2/355; 0.6%).
  
  
  CONCLUSIONS
  Rare high-level amplifications of therapeutic target genes were found in patients with colon cancer. Although no molecular differences were found between incidences of colon cancer cases in Swiss and Saudi populations, these observations emphasise the urgent need for clinical studies investigating the effect of targeted therapies.
authors.affiliation: Department of Human Cancer Genomic Research, Research Centre at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia. kkuraya@kfshrc.edu.sa
authors.forename: Khawla
authors.initials: K
authors.lastname: Al-Kuraya
authors.forename: Hedvika
authors.initials: H
authors.lastname: Novotny
authors.forename: Prashant
authors.initials: P
authors.lastname: Bavi
authors.forename: Abdul K
authors.initials: AK
authors.lastname: Siraj
authors.forename: Shahab
authors.initials: S
authors.lastname: Uddin
authors.forename: Adnan
authors.initials: A
authors.lastname: Ezzat
authors.forename: Nasser Al
authors.initials: NA
authors.lastname: Sanea
authors.forename: Fouad
authors.initials: F
authors.lastname: Al-Dayel
authors.forename: Hadeel
authors.initials: H
authors.lastname: Al-Mana
authors.forename: Salwa S
authors.initials: SS
authors.lastname: Sheikh
authors.forename: Martina
authors.initials: M
authors.lastname: Mirlacher
authors.forename: Coya
authors.initials: C
authors.lastname: Tapia
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.forename: Guido
authors.initials: G
authors.lastname: Sauter
authors.forename: Luigi
authors.initials: L
authors.lastname: Terracciano
authors.forename: Luigi
authors.initials: L
authors.lastname: Tornillo
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D056741:Cyclin D; D016213:Cyclins / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005500:Follow-Up Studies; D005784:Gene Amplification; D018773:Genes, erbB-1 / Q000235:genetics; D018734:Genes, erbB-2; D016259:Genes, myc / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D009367:Neoplasm Staging; D000075223:Poly-ADP-Ribose Binding Proteins; D011379:Prognosis; D040081:Protein Array Analysis / Q000379:methods; D011519:Proto-Oncogenes; D016019:Survival Analysis
chemical_list: D000951:Antigens, Neoplasm; D056741:Cyclin D; D016213:Cyclins; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human