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Deletion at 3p25.3–p23 is frequently encountered in endocrine pancreatic tumours and is associated with metastatic progression
Author(s) -
Barghorn André,
Komminoth Paul,
Bachmann Daniela,
Rütimann Katrin,
Saremaslani Parvin,
MulettaFeurer Seraina,
Perren Aurel,
Roth Jürgen,
Heitz Philipp U.,
Speel Ernst J. M.
Publication year - 2001
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.886
Subject(s) - loss of heterozygosity , biology , fluorescence in situ hybridization , chromosome , allele , cancer research , pathogenesis , pathology , pancreas , gene , genetics , medicine , immunology , endocrinology
Abstract For several reasons, chromosome 3p is thought to be involved in the pathogenesis of sporadic endocrine pancreatic tumours (EPTs): von Hippel–Lindau's disease (VHL gene at 3p25.5) is associated with EPTs; 3p is frequently involved in solid human tumours; and comparative genomic hybridization has identified frequent losses at 3p in EPTs. This study investigated 99 benign and malignant tumours, including 20 metastases, from 82 patients, by microsatellite loss of heterozygosity (LOH) analysis and fluorescence in situ hybridization (FISH) in order to evaluate the importance of chromosome 3p deletions in the molecular pathogenesis and biological behaviour of EPTs, to elaborate a common region of deletion, and to narrow down putative tumour suppressor 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 significantly higher in malignant than in benign neoplasms (70.2% versus 28.0%; p =0.001). In addition, a strong correlation was found between the loss 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 the entire short arm of chromosome 3 with tumour progression. Furthermore, FISH 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. Copyright © 2001 John Wiley & Sons, Ltd.