PMID- 15947114
OWN - NLM
STAT- MEDLINE
DCOM- 20050822
LR  - 20061115
IS  - 1351-0088 (Print)
IS  - 1351-0088 (Linking)
VI  - 12
IP  - 2
DP  - 2005 Jun
TI  - Chromosomal instability predicts metastatic disease in patients with insulinomas.
PG  - 435-47
AB  - Endocrine pancreatic tumors (EPTs) comprise a highly heterogeneous group of 
      tumors with different clinical behavior and genetic makeup. Insulinomas represent 
      the predominant syndromic subtype of EPTs. The metastatic potential of 
      insulinomas can frequently not be predicted using histopathological criteria, and 
      also molecular markers indicating malignant progression are unreliable because of 
      the small number of cases per subtype studied so far. For the identification of 
      reliable indicators of metastatic disease, we investigated 62 sporadic 
      insulinomas (44 benign and 18 tumors with metastases) by means of comparative 
      genomic hybridization (CGH). In addition, the role of MEN1 (multiple endocrine 
      neoplasia type 1) gene mutations was determined to assess specific chromosomal 
      alterations associated with dysfunction of this endocrine tumor-related tumor 
      suppressor gene. Only one case with a somatic MEN1 mutation was identified 
      (1527del7bp), indicating that the MEN1 gene plays a minor pathogenic role in 
      sporadic insulinomas. CGH analysis revealed that the total number of aberrations 
      per tumor differs strongly between the benign and the malignant group (4.2 vs 
      14.1; P<0.0001). Furthermore, chromosome 9q gain was found to be the most 
      frequent aberration in both benign and malignant insulinomas, whereas chromosome 
      6q losses and 12q, 14q and 17pq gains are strongly associated with metastatic 
      disease. Our study shows that chromosomal instability, as defined by > or =5 
      gains together with > or =5 losses, or total number of gains and losses > or =8, 
      rather than parameters such as tumor size and proliferation index, is the most 
      powerful indicator for the development of metastatic disease in patients with 
      sporadic insulinoma.
FAU - Jonkers, Y M H
AU  - Jonkers YM
AD  - Department of Molecular Cell Biology Box 17, Research Institute for Growth and 
      Development, University of Maastricht, PO Box 616, 6200 MD, Maastricht, The 
      Netherlands. Y.Jonkers@MOLCELB.unimaas.nl
FAU - Claessen, S M H
AU  - Claessen SM
FAU - Perren, A
AU  - Perren A
FAU - Schmid, S
AU  - Schmid S
FAU - Komminoth, P
AU  - Komminoth P
FAU - Verhofstad, A A
AU  - Verhofstad AA
FAU - Hofland, L J
AU  - Hofland LJ
FAU - de Krijger, R R
AU  - de Krijger RR
FAU - Slootweg, P J
AU  - Slootweg PJ
FAU - Ramaekers, F C S
AU  - Ramaekers FC
FAU - Speel, E-J M
AU  - Speel EJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - England
TA  - Endocr Relat Cancer
JT  - Endocrine-related cancer
JID - 9436481
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
SB  - IM
MH  - Adult
MH  - Chromosomal Instability/*genetics
MH  - Diagnosis, Differential
MH  - Female
MH  - Humans
MH  - Insulinoma/*diagnosis/genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Neoplasm Metastasis
MH  - Nucleic Acid Hybridization
MH  - Pancreatic Neoplasms/*diagnosis/genetics/pathology
MH  - Prognosis
MH  - Proto-Oncogene Proteins/*genetics
EDAT- 2005/06/11 09:00
MHDA- 2005/08/23 09:00
CRDT- 2005/06/11 09:00
PHST- 2005/06/11 09:00 [pubmed]
PHST- 2005/08/23 09:00 [medline]
PHST- 2005/06/11 09:00 [entrez]
AID - 12/2/435 [pii]
AID - 10.1677/erc.1.00960 [doi]
PST - ppublish
SO  - Endocr Relat Cancer. 2005 Jun;12(2):435-47. doi: 10.1677/erc.1.00960.