Because aberrant methylation of ppENK or p16 was more often detected in similar grade PanINs from patients with pancreatic carcinoma than in those with other pancreatic diseases, it may be a useful indicator of the potential malignancy of epithelial cells of the pancreas.
The effect was specific to pRB depletion because two other human pancreatic cancer cell lines that retained high pRB expression after p16 transfection were resistant to chemotherapy-induced apoptosis.
Activation of the proto-oncogene K-Ras and inactivation of the tumour suppressor gene loci INK4a, p53 and SMAD4 are characteristic for pancreatic cancer.
Additionally, we analysed the aberrant methylation frequency of cell cycle inhibitor p16(INK4a) and K-ras gene mutations in the pancreatic samples. p16 inactivation was detected in 43% of adenocarcinomas, in 17% of neuroendocrine tumors, in 18% of pancreatitis and in 63% of pancreas cancer cell lines.
The incidence of p16 mutations was 2 (9%) in 22 cases of pancreatic carcinoma with strongly positive staining, 4 (17%) in 24 with weakly positive staining, and 3 (21%) in 14 with negative staining.
The current results provide additional evidence that multiple nevi, melanoma, or pancreatic carcinoma may be inherited as autosomal-dominant traits in families known to harbor CDKN2A mutations.
We investigated the association between INK4/ARF alterations and the occurrence of pancreatic cancer in MF and in sporadic pancreatic cancer (SPC) patients.
There is also an increased risk of pancreatic cancer in a subset of families with mutations, however, the precise relationship between the CDKN2A gene and pancreatic cancer remains unknown.
A group I intron ribozyme was designed to trans-splice the 2 base-deleted p16 transcripts with the wild-type sequence in a pancreatic cancer cell line, which originally produced no p16.
In this study we examine whether combining Ad-mediated delivery of p53 or p16(INK4A) with clinically relevant chemotherapeutic drugs has therapeutic potential for pancreatic cancer.
Three known tumor suppressor genes, p16/CDKN2, BRCA2, and p53, all of which are important in the development of pancreatic carcinoma and frequently are involved in a variety of cancer syndromes, were analyzed.
This article traces the historical aspects of hereditary cancer dealing with identification and ultimate molecular genetic confirmation of commonly occurring cancers, particularly of the colon in the case of familial adenomatous polyposis and its attenuated form, both due to the APC germline mutation; the Lynch syndrome due to mutations in mismatch repair genes, the most common of which were found to be MSH2, MLH1, and MSH6 germline mutations; the hereditary breast-ovarian cancer syndrome with BRCA1 and BRCA2 germline mutations; the Li-Fraumeni (SBLA) syndrome due to the p53 mutation; and the familial atypical multiple mole melanoma in association with pancreatic cancer due to the CDKN2A (p16) germline mutation.
Using LD-PCR, mutations in p53 and/or p16 were found in the pancreatic juice of 12 of 20 individuals with pancreatic cancer compared to only 1 of 8 patients with chronic pancreatitis, 0 of 8 individuals without evidence of pancreatic disease (p<0.02).