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 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.
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.
The expression of the nuclear and cytoplasmic forms of p16 represent two independent mechanisms, and both seemed to control proliferation in response to oncogenic stimuli, protecting the cell from malignant transformation in BRAF-mutated GISTs.
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.
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.
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.
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.
To investigate the p16 protein expression and promoter methylation of p16 gene in Ca-ex-PA and their roles in the malignant transformation of pleomorphic adenoma to Ca-ex-PA.
These results imply that alterations of the cell-cycle checkpoint controlling proteins p27(KIP1), p16(INK4a), and RB1 may exert a profound effect in malignant transformation in BPDCN.
HMEC that express p16INK4A and vHMEC that do not, were transduced with constitutively active Ha-rasV12 and subsequently exposed to serum to determine whether signals from the cellular microenvironment could cooperate with ras to promote the malignant transformation of vHMEC.
We thus conclude that methylation of the p16 gene promoter shows promise as a predictor for malignant transformation (Fisher's exact, P = 0.002) in a subset of patients.
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.
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.
It has been suggested that the up-regulation of the tumour suppressor p16 gene and induction of senescence protect the phenotype of psoriatic involved skin from malignant transformation.