This review briefly summarizes the current information on the pRb1-cyclin D1-cdk4/6-p16(INK4A) alterations in sporadic uterine cancer, placing emphasis on the influence on the dualistic model of endometrial carcinogenesis.
p16(INK4a) alterations are considered to be an early event in pancreatic tumorigenesis and have been described in duct lesions adjacent to pancreatic cancers.
The formation of lung tumors by these chemicals involved mutations in the K-ras cancer gene and loss of heterozygosity in the region of K-ras on distal chromosome 6, while alterations in p53 and p16 were implicated in brain tumorigenesis.
In our study the expression of p16 protein was absent or low in renal cell cancer samples, suggesting that loss of the p16 gene may be involved in renal cell carcinogenesis.
From the data, it can be argued that p16/CDKN2 and p53 mutations are relatively late occurrences in human oral tumorigenesis and that genetic alterations of the ras genes may not play a significant role in squamous neoplasia.
Alterations of the p16INK4 gene were detected in 6 (2 insertions and 4 homozygous deletions) of 22 metastatic non-small cell lung cancers (NSCLCs; 27%), but none were detected in 25 primary NSCLCs, 15 primary small cell lung cancers (SCLCs), or 9 metastatic SCLCs, indicating that mutation in the p16INK4 gene is a late event in NSCLC carcinogenesis.
We conclude that during oral carcinogenesis homozygous deletion of exon 1alpha of the CDKN2A gene is common but that deletion of exon 2 and 1beta is less frequent.
Studies of biochemical and biological functions of both wild-type and mutant proteins are central to our understanding of the role of p16INK4a mutations in tumorigenesis, a summary of these studies is also included in the present update.
With the successful application of bio-cell chip technique, we found that the deletion of p16 contributed to the oncogenesis in acute leukemia, but not in chronic leukemia.
The combination of MMR gene mutations and abnormalities of p16 or other molecular pathways is needed to induce melanocytic carcinogenesis in a familial setting as well as in sporadic MM.
Although two-hit inactivation was not evident in any of the mutation cases and further investigation would be needed to elucidate the role of altered p16INK4, these results suggest that the p16INK4 gene mutations are relatively frequent and its inactivation might be important in ampullary carcinogenesis.
Although some LM-BN share several significant genetic alterations with leiomyosarcoma, including p16 and p53, the underlying tumorigenesis of LM-BN remains largely unknown.
The relatively low rate of p16 mutation compared with the frequency of LOH suggests the possible involvement of another tumour suppressor gene located on chromosome 9 in oesophageal carcinogenesis.
The aim of this study was to investigate promoter methylation of certain tumor suppressor genes, Cyclin-dependent kinase inhibitor 2A (p16) and Adenomatous polyposis coli (APC), which take part in gastrointestinal tumorigenesis.
The present study used the ferric nitrilotriacetate (Fe-NTA)-induced rat renal carcinogenesis model to determine whether oxidative damage can cause specific allelic loss of p16 (INK4A).
This study showed that p16 and MDM2 polymorphisms do not play a decisive role in tumorigenesis, but some genotypes of these polymorphisms might be associated with follow-up characteristics of prolactinoma.
These results suggest that p16INK4A gene alterations may play a certain role for lung carcinogenesis in co-operation with either K-ras or p53 gene alterations.
Thus, unlike the p16 and p15 tumor suppressor genes, which are frequently deleted and inactivated in brain lymphoma and represent a striking contrast to systemic lymphoma, MMAC1 may not play an important role in carcinogenesis in this tumor, as in the systemic counterpart.
The CDKN2A Database improves upon existing resources by: 1) including both somatic mutations and germline variants, thereby adding the perspective of somatic cell carcinogenesis to that of hereditary cancer predisposition; 2) including information that assists with the interpretation of allelic variants, such as other primary data (sequences, structures, alignments, functional measurements, and literature references) and annotations (extensive text, figures, and a tree-based phylogenetic classification); and 3) providing the information in a format that allows a user to either download the database or to easily manipulate it online.
We investigated the prevalence of single nucleotide polymorphisms in the p16 gene (C540G) and the cyclin D1 gene (G870A), both known to regulate function in G1 arrest and therefore, may play an important role in carcinogenesis.