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Chromosomal instability predicts metastatic disease in patients with insulinomas.
Endocr Relat Cancer. 2005 Jun; 12(2):435-47.ER

Abstract

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.

Authors+Show Affiliations

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.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

15947114

Citation

Jonkers, Y M H., et al. "Chromosomal Instability Predicts Metastatic Disease in Patients With Insulinomas." Endocrine-related Cancer, vol. 12, no. 2, 2005, pp. 435-47.
Jonkers YM, Claessen SM, Perren A, et al. Chromosomal instability predicts metastatic disease in patients with insulinomas. Endocr Relat Cancer. 2005;12(2):435-47.
Jonkers, Y. M., Claessen, S. M., Perren, A., Schmid, S., Komminoth, P., Verhofstad, A. A., Hofland, L. J., de Krijger, R. R., Slootweg, P. J., Ramaekers, F. C., & Speel, E. J. (2005). Chromosomal instability predicts metastatic disease in patients with insulinomas. Endocrine-related Cancer, 12(2), 435-47.
Jonkers YM, et al. Chromosomal Instability Predicts Metastatic Disease in Patients With Insulinomas. Endocr Relat Cancer. 2005;12(2):435-47. PubMed PMID: 15947114.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chromosomal instability predicts metastatic disease in patients with insulinomas. AU - Jonkers,Y M H, AU - Claessen,S M H, AU - Perren,A, AU - Schmid,S, AU - Komminoth,P, AU - Verhofstad,A A, AU - Hofland,L J, AU - de Krijger,R R, AU - Slootweg,P J, AU - Ramaekers,F C S, AU - Speel,E-J M, PY - 2005/6/11/pubmed PY - 2005/8/23/medline PY - 2005/6/11/entrez SP - 435 EP - 47 JF - Endocrine-related cancer JO - Endocr Relat Cancer VL - 12 IS - 2 N2 - 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. SN - 1351-0088 UR - https://www.unboundmedicine.com/medline/citation/15947114/Chromosomal_instability_predicts_metastatic_disease_in_patients_with_insulinomas_ L2 - https://erc.bioscientifica.com/doi/10.1677/erc.1.00960 DB - PRIME DP - Unbound Medicine ER -