PMID- 11523053
OWN - NLM
STAT- MEDLINE
DCOM- 20010927
LR  - 20191105
IS  - 0022-3417 (Print)
IS  - 0022-3417 (Linking)
VI  - 194
IP  - 4
DP  - 2001 Aug
TI  - Deletion at 3p25.3-p23 is frequently encountered in endocrine pancreatic tumours 
      and is associated with metastatic progression.
PG  - 451-8
AB  - 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.
CI  - Copyright 2001 John Wiley & Sons, Ltd.
FAU - Barghorn, A
AU  - Barghorn A
AD  - Department of Pathology, University of Zurich, Schmelzbergstrasse 12, CH-8091 
      Zurich, Switzerland. andre.barghorn@pty.usz.ch
FAU - Komminoth, P
AU  - Komminoth P
FAU - Bachmann, D
AU  - Bachmann D
FAU - Rutimann, K
AU  - Rutimann K
FAU - Saremaslani, P
AU  - Saremaslani P
FAU - Muletta-Feurer, S
AU  - Muletta-Feurer S
FAU - Perren, A
AU  - Perren A
FAU - Roth, J
AU  - Roth J
FAU - Heitz, P U
AU  - Heitz PU
FAU - Speel, E J
AU  - Speel EJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
SB  - IM
MH  - Adult
MH  - Aged
MH  - *Chromosomes, Human, Pair 3
MH  - Disease Progression
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Loss of Heterozygosity
MH  - Male
MH  - Microsatellite Repeats
MH  - Middle Aged
MH  - Neoplasm Metastasis
MH  - Pancreatic Neoplasms/*genetics
EDAT- 2001/08/28 10:00
MHDA- 2001/09/28 10:01
CRDT- 2001/08/28 10:00
PHST- 2001/08/28 10:00 [pubmed]
PHST- 2001/09/28 10:01 [medline]
PHST- 2001/08/28 10:00 [entrez]
AID - 10.1002/path.886 [pii]
AID - 10.1002/path.886 [doi]
PST - ppublish
SO  - J Pathol. 2001 Aug;194(4):451-8. doi: 10.1002/path.886.