A similar effect of P16 hydroxymethylation and true-methylation on the prediction of malignant transformation of oral epithelial dysplasia: observation from a prospective study.
The majority (5/8) of MPNSTs in our analyses demonstrated homozygous or heterozygous deletions of CDKN2A, which may represent an early event following NF1 LOH in the malignant transformation of Schwann cells from plexiform neurofibroma to MPNST.
In mouse melanoma models with specific induced gene mutations including mutations of the Braf, Pten, and Cdkn2a genes, viral infection correlated with the extent of malignant transformation.
Some bladder primary tumors and some bladder and melanoma tumor cell lines contain mutations in both P16 and P53 at frequencies that suggest that p53 and p16 function in different pathways, each of which is important in suppressing malignant transformation.
We also examined deletion of cyclin-dependent kinase inhibitor 4 (INK4) genes and mutation of p53 gene in combination with changes in the HTLV-I genome in acute type ATL to test whether host genetic changes promoted the malignant transformation of ATL cells that carry putative CTL escape mutations.
The aim of the study was to analyze the correlation between the expression of p16 as a surrogate of HPV infection in analyzed histopathological material and epidemiological variables, recurrences or malignant transformation.
Inactivation of the p16(INK4a)/Rb pathway may allow continuous cell division and critical telomere shortening, which induce genome instability, finally leading to malignant transformation.
This study evaluated INK4a/ARF locus alterations in 26 patients (28 samples) deemed to be at increased risk for malignant transformation to squamous cell carcinoma due to the diagnosis of severe oral epithelial dysplasia.
It has been shown that the induction of p16(Ink4a) in premalignant lesions and its loss during malignant transformation is an important mechanism in the carcinogenesis of several tumours.
Methylation of the DAPK and p16 genes, although not sufficient to dictate prognosis of the disease, should not be underestimated because it may form part of a process of genetic and epigenetic alterations that in the future could become relevant to malignant transformation.
Results of this study suggest that two different genetic alterations, the inactivation of the p16 gene and genetic instability, play roles in the malignant transformation of carcinoma in pleomorphic adenoma.
Our study suggests that: (1) polysomy 6 and p16 deletion may contribute to adenomatous change of IPMN; (2) polysomy 7, polysomy 18, p16 deletion, and p53 deletion play roles in malignant transformation of noninvasive IPMN; and (3) polysomy 7 and p53 deletion may be excellent diagnostic markers for invasive IPMN.
The aim of this study is to investigate the relationship between p16 methylation and malignant transformation of human gastric dysplasia (DYS) based on follow-up endoscopic screening in a high-risk population.
We conclude (1) that p16(INK4a) epigenetic inactivation most likely represents an early event, insufficient for malignant transformation, that may occur in clinically benign lesions such as LS; (2) that lack of pRb was only detected in fewer than one quarter of the carcinomas and could be considered a late secondary event; and (3) that cyclin-D1, which was overexpressed in VC and VIN, could contribute to the malignant transformation in association with p16 hypermethylation.