Low frequency of p(16INK4a) alterations in insulinomas

Background/Aims: The molecular mechanisms contributing to the tumorigenesis of insulinomas are poorly understood. Disruption of the cell cycle due to inactivation of the p16(INK4a) tumor-suppressor gene was identified in a va riety of human tumors, including gastrinomas and nonfunctioning endocrine p ancreatic carcinomas. In this study the role of p16(INK4a) i, the tumorigen esis of insulinomas was evaluated. Merhods: Seventeen insulinomas (14 benig n, 3 malignant) were analyzed for genetic alterations in the p16(INK4a) tum or-suppressor gene by SSCP, PCR-based deletion and methylation-specific ass ays, p16 expression was determined by immunohistochemistry. Results: One ma lignant insulinoma showed a homozygous deletion of p16(INK4a) and another t wo benign insulinomas revealed aberrant methylation of the p16(INK4a) promo ter region. All three tumors lacked p16 expression according to immunohisto chemistry. None of the insulinomas carried intragenic p16(INK4a) mutations. In total, 17% of insulinomas had p16(INK4a) alterations. Conclusions: The p16(INK4a) tumor-suppressor gene contributes to tumorigenesis in only a sma ll subset of insulinomas. Copyright (C) 2000 S. Karger AG. Basel.