Alterations of tumor suppressor gene p16INK4a in pancreatic ductal carcinoma.
BACKGROUND
Cell cycle inhibitor and tumor suppressor gene p16/MTS-1 has been reported to be altered in a variety of human tumors. The purpose of the study was to evaluate primary pancreatic ductal adenocarcinomas for potentially inactivating p16 alterations.


METHODS
We investigated the status of p16 gene by polymerase chain reaction (PCR), nonradioisotopic single strand conformation polymorphism (SSCP), DNA sequencing and hypermethylation analysis in 25 primary resected ductal adenocarcinomas. In addition, we investigated p16 protein expression in these cases by immunohistochemistry (IHC) using a monoclonal antibody clone (MS-887-PO).


RESULTS
Out of the 25 samples analyzed and compared to normal pancreatic control tissues, the overall frequency of p16 alterations was 80% (20/25). Aberrant promoter methylation was the most common mechanism of gene inactivation present in 52% (13/25) cases, followed by coding sequence mutations in 16% (4/25) cases and presumably homozygous deletion in 12% (3/25) cases. These genetic alterations correlated well with p16 protein expression as complete loss of p16 protein was found in 18 of 25 tumors (72%).


CONCLUSIONS
These findings confirm that loss of p16 function could be involved in pancreatic cancer and may explain at least in part the aggressive behaviour of this tumor type.
Department of General Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India. jyotika_attri@yahoo.com
Jyotika
J
Attri
Radhika
R
Srinivasan
Siddhartha
S
Majumdar
Bishan Dass
BD
Radotra
Jaidev
J
Wig
D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000172:deficiency / Q000378:metabolism; D019175:DNA Methylation; D005260:Female; D017353:Gene Deletion; D020868:Gene Silencing; D019942:Genes, p16; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D013194:Staining and Labeling
D019941:Cyclin-Dependent Kinase Inhibitor p16