Deletion at 3p25.3-p23 is frequently encountered in endocrine pancreatic tumours and is associated with metastatic progression

For several reasons, chromosome 3p is thought to be involved in the pathoge nesis of sporadic endocrine pancreatic tumours (EPTs): von Hippel-Lindau's disease (VHL gene at 3p25.5) is associated with EPTs; 3p is frequently invo lved in solid human tumours; and comparative genomic hybridization has iden tified frequent losses at 3p in EPTs. This study investigated 99 benign and malignant tumours, including 20 metastases, from 82 patients, by microsate llite loss of heterozygosity (LOH) analysis and fluorescence in situ hybrid ization (FISH) in order to evaluate the importance of chromosome 3p deletio ns in the molecular pathogenesis and biological behaviour of EPTs, to elabo rate a common region of deletion, and to narrow down putative tumour suppre ssor gene loci. Allelic losses of 3p were found in 58/99 (58.6%) of tumours in 45/82 (54.9%) patients; analysis of seven microsatellite markers (3p26- p21) revealed a common region of LOH at 3p25.3-p23. The LOH frequency was s ignificantly higher in malignant than in benign neoplasms (70.2%, versus 28 .0%; p = 0.001). In addition, a strong correlation was found between the lo ss of alleles on chromosome 3p and clinically metastatic disease (LOH of 73 .7% in metastasizing versus 41.5% in non-metastasizing tumours; p = 0.008). EPTs from these patients showed a tendency towards losing large parts or t he entire short arm of chromosome 3 with tumour progression. Furthermore, F ISH analysis revealed complete loss of chromosome 3 in ten out of 37 EPTs ( 27%). These results indicate that a putative tumour suppressor gene at 3p25 .3-p23 may play a role in the oncogenesis of sporadic EPTs and that losses of larger centromeric regions are associated with metastatic progression. C opyright (C) 2001 John Wiley & Sons, Ltd.