Low frequency of p16(INK4a) alterations in insulinomas.
OBJECTIVE
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 variety of human tumors, including gastrinomas and nonfunctioning endocrine pancreatic carcinomas. In this study the role of p16(INK4a) in the tumorigenesis of insulinomas was evaluated.


METHODS
Seventeen insulinomas (14 benign, 3 malignant) were analyzed for genetic alterations in the p16(INK4a) 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 p16(INK4a) and another two benign insulinomas revealed aberrant methylation of the p16(INK4a) promoter region. All three tumors lacked p16 expression according to immunohistochemistry. 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 small subset of insulinomas.
Bartsch
D K
DK
Department of Surgery, Philipps University, Marburg, Germany. bartsch@mailer.uni-marburg.de
Kersting
M
M
Wild
A
A
Ramaswamy
A
A
Gerdes
B
B
Schuermann
M
M
Simon
B
B
Rothmund
M
M
D002453:Cell Cycle / Q000235:genetics*; D002471:Cell Transformation, Neoplastic; D002872:Chromosome Deletion; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D019942:Genes, p16 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D007340:Insulinoma / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic
D004273:DNA, Neoplasm