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A Novel Insulinoma Tumor Suppressor Gene Locus on Chromosome 22q with Potential Prognostic Implications

Departments of General Surgery (A.W., P.L., B.C., D.K.B.) and Pathology (A.R.), Philipps University of Marburg, D-35043 Marburg, Germany

Address all correspondence and requests for reprints to: Detlef K. Bartsch, M.D., Department of General Surgery, Philipps University of Marburg, Baldingerstrasse, D-35043 Marburg, Germany. E-mail: bartsch{at}mailer.uni-marburg.de

Abstract

The molecular mechanisms contributing to the tumorigenesis of insulinomas are still poorly understood. As moderate to high rates of LOH have been found on chromosome 22q in gastrinomas, we performed a finer deletion mapping study of chromosome 22q with 8 microsatellite markers in 15 insulinomas (4 malignant and 11 benign). Fourteen of 15 (93%) insulinomas revealed LOH on chromosome 22q, whereas the shortest region of overlap implicated a deletion of approximately 700 kb at 22q12.1-q12.2 with an LOH rate of up to 57% (8 of 14). Although the expressed sequence tag marker A006E25 that is localized in the hSNF5/INI1 gene on 22q11.2 revealed LOH in 50% of informative cases (7 of 14), no alterations in this gene could be identified by single strand conformational polymorphism analysis, direct DNA sequencing, or RNA expression analysis. Remarkably, the four malignant tumors showed a common deleted region between markers D22S345 and D22S1144 compared with none of the 11 benign insulinomas.

The observed high frequency of chromosome 22q12 deletions in insulinomas is suggestive for a region compatible with harboring a tumor suppressor gene. The hSNF5/INI1 gene is most likely not the candidate gene, because no alterations could be identified. The distinct pattern of allelic loss identified in this chromosomal region appears to be an attractive candidate marker for further evaluation with regard to the discrimination between benign and malignant insulinomas.

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