title: Multiple genetic lesions in laryngeal squamous cell carcinomas.
abstract: BACKGROUND
  To understand the molecular pathogenesis of laryngeal squamous cell carcinomas (LSCCs), this study investigated the involvement of various protooncogene loci (bcl-1, int-2, c-erbB-1, c-myc, ras) and the p53 tumor suppressor gene in 18 patients with LSCC (15 at clinical presentation, 3 in clinical relapse).
  
  
  METHODS
  For all patients, the mutations affecting the p53 and the H-, K-, and N-ras genes were evaluated by polymerase chain reaction (PCR), single-strand conformation polymorphism, and the direct sequencing of PCR-amplified fragments. The bcl-1, int-2, c-erbB-1, and c-myc loci of 15 patients were investigated using Southern blot analysis.
  
  
  RESULTS
  A mutation of the p53 gene was detected in 5/18 patients (approximately 28%), bcl-1 locus amplification in 4/15 (approximately 26%), c-erbB-1 locus amplification in 2/15 (approximately 13%), and c-myc locus amplification in 1/15 (approximately 6%). The simultaneous presence of more than one genetic lesion was observed in four patients; two showed int-2/bcl-1 coamplification, and two int-2/c-erbB-1 coamplification, one of whom also showed a p53 gene mutation. A novel p53 mutation involving the splice acceptor site of exon 6 was detected in one patient. Two of the five patients positive for p53 mutations had clinical relapses of primary tumors. bcl-1 locus amplification only was observed in patients with lymph node metastases (4/6). All but one of the patients with molecular genetic lesions showed a peculiar infiltrating pattern.
  
  
  CONCLUSIONS
  Overall, these results show that alterations of known protooncogenes and the p53 tumor suppressor gene are involved in a large proportion of LSCCs (11/18; approximately 60%) and may suggest that distinct molecular pathways occur in the pathogenesis of these tumors.
authors.affiliation: Laboratorio di Ematologia Sperimentale e Genetica Molecolare, Universita di Milano, Ospedale, Maggiore, Milan, Italy.
authors.forename: N S
authors.initials: NS
authors.lastname: Fracchiolla
authors.forename: L
authors.initials: L
authors.lastname: Pignataro
authors.forename: P
authors.initials: P
authors.lastname: Capaccio
authors.forename: D
authors.initials: D
authors.lastname: Trecca
authors.forename: A
authors.initials: A
authors.lastname: Boletini
authors.forename: A
authors.initials: A
authors.lastname: Ottaviani
authors.forename: E
authors.initials: E
authors.lastname: Polli
authors.forename: A T
authors.initials: AT
authors.lastname: Maiolo
authors.forename: A
authors.initials: A
authors.lastname: Neri
mesh_terms: D000368:Aged; D001483:Base Sequence; D015139:Blotting, Southern; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D019938:Cyclin D1; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis*; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000235:genetics; D018815:Genes, erbB / Q000235:genetics; D016259:Genes, myc / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011519:Proto-Oncogenes / Q000235:genetics*
chemical_list: D004273:DNA, Neoplasm; C496444:FGF3 protein, human; D051518:Fibroblast Growth Factor 3; D011518:Proto-Oncogene Proteins; D019938:Cyclin D1; D005346:Fibroblast Growth Factors