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 journalArticle

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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

Fingerprint

Squamous Cell Carcinoma
Mutation
ras Genes
p53 Genes
Tumor Suppressor Genes
Recurrence
Polymerase Chain Reaction
RNA Splice Sites
Southern Blotting
Molecular Biology
Exons
Neoplasms
Lymph Nodes
Neoplasm Metastasis

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

Cite this

Multiple genetic lesions in laryngeal squamous cell carcinomas. / Fracchiolla, N. S.; Pignataro, L.; Capaccio, P.; Trecca, D.; Boletini, A.; Ottaviani, A.; Polli, E.; Maiolo, A. T.; Neri, A.

In: Cancer, Vol. 75, No. 6, 1995, p. 1292-1301.

Research output: Contribution to journalArticle

Fracchiolla, N. S. ; Pignataro, L. ; Capaccio, P. ; Trecca, D. ; Boletini, A. ; Ottaviani, A. ; Polli, E. ; Maiolo, A. T. ; Neri, A. / Multiple genetic lesions in laryngeal squamous cell carcinomas. In: Cancer. 1995 ; Vol. 75, No. 6. pp. 1292-1301.
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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.",
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AU - Fracchiolla, N. S.

AU - Pignataro, L.

AU - Capaccio, P.

AU - Trecca, D.

AU - Boletini, A.

AU - Ottaviani, A.

AU - Polli, E.

AU - Maiolo, A. T.

AU - Neri, A.

PY - 1995

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N2 - 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.

AB - 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.

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