title: Prognostic impact of array-based genomic profiles in esophageal squamous cell cancer.
abstract: BACKGROUND
  Esophageal squamous cell carcinoma (ESCC) is a genetically complex tumor type and a major cause of cancer related mortality. Although distinct genetic alterations have been linked to ESCC development and prognosis, the genetic alterations have not gained clinical applicability. We applied array-based comparative genomic hybridization (aCGH) to obtain a whole genome copy number profile relevant for identifying deranged pathways and clinically applicable markers.
  
  
  METHODS
  A 32 k aCGH platform was used for high resolution mapping of copy number changes in 30 stage I-IV ESCC. Potential interdependent alterations and deranged pathways were identified and copy number changes were correlated to stage, differentiation and survival.
  
  
  RESULTS
  Copy number alterations affected median 19% of the genome and included recurrent gains of chromosome regions 5p, 7p, 7q, 8q, 10q, 11q, 12p, 14q, 16p, 17p, 19p, 19q, and 20q and losses of 3p, 5q, 8p, 9p and 11q. High-level amplifications were observed in 30 regions and recurrently involved 7p11 (EGFR), 11q13 (MYEOV, CCND1, FGF4, FGF3, PPFIA, FAD, TMEM16A, CTTS and SHANK2) and 11q22 (PDFG). Gain of 7p22.3 predicted nodal metastases and gains of 1p36.32 and 19p13.3 independently predicted poor survival in multivariate analysis.
  
  
  CONCLUSIONS
  aCGH profiling verified genetic complexity in ESCC and herein identified imbalances of multiple central tumorigenic pathways. Distinct gains correlate with clinicopathological variables and independently predict survival, suggesting clinical applicability of genomic profiling in ESCC.
authors.affiliation: Department of Oncology, Lund University Hospital, 221 85 Lund, Sweden. Ana.Carneiro@med.lu.se
authors.forename: Ana
authors.initials: A
authors.lastname: Carneiro
authors.forename: Anna
authors.initials: A
authors.lastname: Isinger
authors.forename: Anna
authors.initials: A
authors.lastname: Karlsson
authors.forename: Jan
authors.initials: J
authors.lastname: Johansson
authors.forename: Göran
authors.initials: G
authors.lastname: Jönsson
authors.forename: Pär-Ola
authors.initials: PO
authors.lastname: Bendahl
authors.forename: Dan
authors.initials: D
authors.lastname: Falkenback
authors.forename: Britta
authors.initials: B
authors.lastname: Halvarsson
authors.forename: Mef
authors.initials: M
authors.lastname: Nilbert
mesh_terms: D000368:Aged; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000175:diagnosis* / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D011379:Prognosis
chemical_list: D005819:Genetic Markers