Therefore, deletion or altered regulation of p16INK4a and p15INK4b occur concomitantly with the loss of differentiation associated with the late spindle stage of tumor progression in mouse skin.
These results indicate that both p16INK4 and p15INK4B gene mutations are associated with tumor progression of a subset of NSCLC, but not of SCLC, and that p15INK4B mutations might also be an early event in the molecular pathogenesis of a subset of NSCLC.
These related cell lines have now been used to evaluate the timing of deletion/mutation of the p16INK4 and p15INK4B genes during tumor progression in melanoma.
However, neither p15INK4B nor p16INK4 were deleted in 12 of 12 primary kidney tumors examined, suggesting that deletion of these genes is not directly involved in the process of renal tumor development but may be related to tumor progression or autonomous growth in vitro.
These results suggest that CDKN2 plays an important role during tumorigenesis or tumor progression in a significant proportion of pancreatic adenocarcinomas.
These results suggest: (a) the involvement of P16INK4 in glioma progression; (b) that mechanisms other than mutation or deletion can down-regulate expression of the p16/CDKN2 gene; and (c) that the balance between CDK4 and its cognate inhibitor, P16INK4, may confer a cell growth advantage and facilitate tumor progression.
The results obtained here for primary non-astrocytic tumors contrast with those previously described for astrocytic tumors where a high frequency of deletions of MTS1 was associated with tumor progression.
We determined the prevalence of allelic loss at 9p21 and mutations in CDKN2 in esophageal adenocarcinomas and investigated the order in which they occurred relative to the development of aneuploidy and cancer during neoplastic progression.
These results indicate that inactivation of the MTS1 gene is not involved in pathogenesis of primary colorectal carcinomas, and that its enhanced expression is, instead, associated with primary colorectal carcinomas, especially markedly in the early stage of tumor progression.
Our results indicate that mts1 expression in human breast cancer cells induces several changes characteristic of malignant phenotype and tumor progression.
This loss of p16/INK4A was found more frequently in cases showing tumor progression from mucosa-associated lymphoid tissue low-grade lymphomas (31 of 37) or follicular lymphomas (4 of 4) into diffuse large B-cell lymphomas.
These results suggest that hypermethylation of the p16INK4a promoter region is a frequent and early occurring event during the process of neoplastic progression in ulcerative colitis.
Inactivation of tumor suppressor genes like p53 and p16 play a key role in tumor progression, with a high incidence of mutations existing for both genes in oral squamous cell carcinomas.
Our preliminary results indicate alterations in the p15 gene were not important in gastric tumorigenesis, while infrequent homozygous deletions in the p16 gene play a limited role in tumour progression of intestinal-type GC.
These data suggest that p16 promoter hypermethylation is a common mechanism of p16 gene inactivation during neoplastic progression in Barrett's esophagus.
In view of the equivocal association of nm23 with the metastatic potential of human cancer, we suspected that the relative expression of h-mts1 and nm23 might reflect tumor progression more accurately than either of them alone.
Notably, TP53 mutation, which has been used as a marker of tumor progression in many human cancers, was less significant in associating with progression in this study (P = 0.04) than was p16 or pRb alteration (P = 0.001).
Components of the pRb pathway which are often altered in tumour progression include the INK4 cyclin-dependent kinase (CDK) inhibitors p16INK4a/ CDKN2A and p15INK4b/CDKN2B, CDK4, D-type cyclins and pRb.
In spite of this possibility, the missense point mutations in conserved region of p53 and p16INK4A genes may indicate the role of p53 and p16INK4A in tumor progression of glomus tumors.
Here, we determine the evolutionary relationships of non-random LOH, TP53 and CDKN2A mutations, CDKN2A CpG-island methylation and ploidy during neoplastic progression.
The simultaneous inactivation of p53 and INK4a-ARF may be linked to the genetic instability caused by XP and could be advantageous for tumor progression.