Pancreatic endocrine tumours: Evidence for a tumour suppressor pathogenesis and for a tumour suppressor gene on chromosome 17p

Stefania Beghelli, Giuseppe Pelosi, Giuseppe Zamboni, Massimo Falconi, Calogero Iacono, Cesare Bordi, Aldo Scarpa

Research output: Contribution to journalArticlepeer-review

Abstract

Two molecular pathways leading to cancer are known. Common-type cancers arise from the 'tumour suppressor' pathway, characterized by gross chromosomal changes and allelic losses (LOH) in an average of 25 per cent or more of randomly chosen chromosomal loci. The 'mutator pathway' has been recognized in a subset of cancers, characterized by widespread microsatellite DNA instability and rarity of chromosomal losses. The present study has investigated 20 pancreatic endocrine tumours (PETs) for loss of heterozygosity (LOH) at seven chromosomal loci (3p14, 7q31-32, 11q13, 13q14, 18q21, 17p13, and 17q21); microsatellite instability; and Ki-ras, N-ras, and p53 gene mutations. LOH was found in an average of 24 per cent of the chromosomal loci analysed. No tumour showed microsatellite instability. Ki- ras and p53 mutations were each found in one case. The frequency of losses was higher in malignant (40 per cent) than in benign (17 per cent) tumours (p=0.009), and the specific chromosome 17p13 LOH was associated with extrapancreatic extension of disease (p=0.007), high proliferative activity (p=0.001), and absence of progesterone receptors (p=0.01). A common deleted region on chromosome 17p13 and the rarity of p53 gene mutations suggest the existence of a novel tumour suppressor gene involved in the pathogenesis of PETs in this chromosomal area.

Original languageEnglish
Pages (from-to)41-50
Number of pages10
JournalJournal of Pathology
Volume186
Issue number1
DOIs
Publication statusPublished - Sep 1998

Keywords

  • Allelotyping
  • BRCA1
  • DCC/DCP4
  • Endocrine tumours
  • FHIT
  • Gene mutations
  • Ki-ras
  • Loss of heterozygosity
  • MEN1
  • N-ras
  • p53
  • Pancreas
  • PAX4
  • RB

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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