Low Frequency of p16INK4a Alterations in Insulinomas
- 1 July 2000
- journal article
- Published by S. Karger AG in Digestion
- Vol. 62 (2-3) , 171-177
- https://doi.org/10.1159/000007810
Abstract
Background/Aims: The molecular mechanisms contributing to the tumorigenesis of insulinomas are poorly understood. Disruption of the cell cycle due to inactivation of the p16INK4a tumor-suppressor gene was identified in a variety of human tumors, including gastrinomas and nonfunctioning endocrine pancreatic carcinomas. In this study the role of p16INK4a in the tumorigenesis of insulinomas was evaluated. Methods: Seventeen insulinomas (14 benign, 3 malignant) were analyzed for genetic alterations in the p16INK4a tumor-suppressor gene by SSCP, PCR-based deletion and methylation-specific assays. p16 expression was determined by immunohistochemistry. Results: One malignant insulinoma showed a homozygous deletion of p16INK4a and another two benign insulinomas revealed aberrant methylation of the p16INK4a promoter region. All three tumors lacked p16 expression according to immunohistochemistry. None of the insulinomas carried intragenic p16INK4a mutations. In total, 17% of insulinomas had p16INK4a alterations. Conclusions: The p16INK4a tumor-suppressor gene contributes to tumorigenesis in only a small subset of insulinomas.Keywords
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