title: ALK gene copy number in lung cancer: Unspecific polyploidy versus specific amplification visible as double minutes.
abstract: BACKGROUND
  Gains of a gene due to DNA polyploidy versus amplification of the specific locus are distinct molecular alterations in tumors.
  
  
  OBJECTIVE
  We quantified copy number gains of ALK gene due to unspecific polyploidy versus amplifications of the specific locus in a series of non-small cell lung cancers.
  
  
  METHODS
  The locus specific ALK copy (LSI) number status was evaluated in 205 cases by FISH. Ratio LSI ALK copy number corrected for control probes CEP2, CEP3 and CEP17 (CEPs) was scored. Amplification of the specific ALK locus was defined when ratio set to ≥ 2 while polyploidy was interpreted when the increase in gene copy resulted < 2 in ratio (LSI/control CEPs).
  
  
  RESULTS
  Twenty one cases (10.2%) showed ≥ 8 ALK signals, 68 cases (33.2%) 3-7 signals and 116 cases (56.6%) a mean of 2 signals. Only 2/21 cases of the cohort harboring ≥ 8 signals showed a ratio ≥ 2 after CEPs correction interpretable as amplified, showing numerous doubled fluorescent spots. All the remaining cases showed a mirrored number of fluorescent spots per each CEPs, interpretable as polyploidy.
  
  
  CONCLUSIONS
  We detected a high prevalence of ALK gene copy number usually due to polyploidy rather than ALK locus amplification, the latter visible prevalently as double minutes.
authors.affiliation: Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Caliò
authors.affiliation: Medical Oncology, University and Hospital Trust, Verona, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Bria
authors.affiliation: Medical Oncology, University and Hospital Trust, Verona, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Pilotto
authors.affiliation: Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors.forename: Eliana
authors.initials: E
authors.lastname: Gilioli
authors.affiliation: Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Nottegar
authors.affiliation: Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors.forename: Albino
authors.initials: A
authors.lastname: Eccher
authors.affiliation: Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Cima
authors.affiliation: Medical Oncology, University and Hospital Trust, Verona, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Santo
authors.affiliation: Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Pedron
authors.affiliation: Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors.forename: Giona
authors.initials: G
authors.lastname: Turri
authors.affiliation: Department of Pathology, Laboratory of Molecular Cytogenetic, University of Helsinki, Helsinki, Finland.
authors.forename: Sakari
authors.initials: S
authors.lastname: Knuutila
authors.affiliation: Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Chilosi
authors.affiliation: Arsenàl, Veneto's Research Center for eHealth Innovation, Veneto, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Vanzo
authors.affiliation: Anatomic Pathology, SacroCuore Hospital, Negrar, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bogina
authors.affiliation: Thoracic Surgery, SacroCuore Hospital, Negrar, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Terzi
authors.affiliation: Medical Oncology, University and Hospital Trust, Verona, Italy.
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Tortora
authors.affiliation: Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
authors.affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Brigham And Women's Hospital, Boston, MA, USA.
authors.forename: Massimo
authors.initials: M
authors.lastname: Loda
authors.affiliation: Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona, Italy.|Anatomic Pathology, Pederzoli Hospital, Peschiera Del Garda, Verona, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Martignoni
authors.affiliation: Department of Diagnostics and Public Health, Anatomic Pathology, University and Hospital Trust, Verona, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Brunelli
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D018307:Neoplasms, Squamous Cell / Q000235:genetics / Q000473:pathology; D011123:Polyploidy; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK gene copy number; amplification; double minutes; gains; polyploidy