Multiple genetic lesions in laryngeal squamous cell carcinomas

N. S. Fracchiolla, L. Pignataro, P. Capaccio, D. Trecca, A. Boletini, A. Ottaviani, E. Polli, A. T. Maiolo, A. Neri

Research output: Contribution to journalArticlepeer-review

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 (≃28%), bcl-1 locus amplification in 4/15 (≃26%), c-erbB-1 locus amplification in 2/15 (≃13%), and c-myc locus amplification in 1/15 (≃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 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; ≃60%) and may suggest that distinct molecular pathways occur in the pathogenesis of these tumors.

Original languageEnglish
Pages (from-to)1292-1301
Number of pages10
JournalCancer
Volume75
Issue number6
DOIs
Publication statusPublished - 1995

Keywords

  • bcl-1, int-2
  • c-erbB-1
  • c-myc
  • H-ras
  • K- ras
  • laryngeal squamous cell carcinomas
  • N-ras
  • p53

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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