title: Genetic model of transformation and neoplastic progression in laryngeal epithelium.
abstract: BACKGROUND
  The aim of this study was to analyze genetic alterations in the transformation-progression model of laryngeal tumors.
  
  
  METHODS
  Copy number changes of 37 genes were analyzed by multiple ligation-dependent probe amplification (MLPA) in 94 tissue samples.
  
  
  RESULTS
  In the smoker normal mucosa group TP53 loss was predominant, whereas in the precursor lesions CDKN2A loss and CDKN2D gain were most frequent. Precursor lesions with progression presented CTNNB1 loss. In the carcinoma group the most common changes were CDKN2A, MLH1, CTNNB1, and CASP6 losses and RECQL4, CCND1, and EMS1 gains. Positive lymph node primary tumors were related to TP53, IL1A, and RB1 losses and STK11 gain. The lymph node metastases differed from their corresponding primary tumor in LMNA, RECQL4, and IGF1R losses, and N33 and CDKN2D gains.
  
  
  CONCLUSIONS
  Genetic changes and new key genes were found to be associated with specific steps. We included new steps, not presented in the classic models: normal mucosa tobacco exposed, positive lymph node primary tumor, and corresponding lymph node metastases.
authors.affiliation: Department of Otorhinolaryngology, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain.
authors.forename: César Álvarez
authors.initials: CÁ
authors.lastname: Marcos
authors.forename: Marta
authors.initials: M
authors.lastname: Alonso-Guervós
authors.forename: Nuria Rodríguez
authors.initials: NR
authors.lastname: Prado
authors.forename: Teresa Sampedro
authors.initials: TS
authors.lastname: Gimeno
authors.forename: Francisco Domínguez
authors.initials: FD
authors.lastname: Iglesias
authors.forename: Mario
authors.initials: M
authors.lastname: Hermsen
authors.forename: José Luis
authors.initials: JL
authors.lastname: Llorente
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D003430:Cross-Sectional Studies; D018450:Disease Progression; D006801:Humans; D007820:Laryngeal Mucosa / Q000473:pathology*; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology*; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology*; D011446:Prospective Studies; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013030:Spain