In conclusion, hMLH1 and O6-MGMT promoter methylation are frequently present in AH, and thus considered to be early events in the carcinogenesis of EC, whereas P16 promoter methylation was mainly present in EC, and not in precursor lesions supporting a late event in the carcinogenesis.
These results indicate that RD deletion and BMI1 overexpression frequently occur in the early stage of oral carcinogenesis and BMI1 overexpression may downregulate the transcription of p16 and p14 through interfering with RD.
Our observation of frequent p14 gene abnormalities (90%) and inactivation (40-60%) was in striking contrast to the same pathological subtype of systemic lymphoma in which p14 gene abnormalities and inactivation were infrequent, suggesting a difference in carcinogenesis between PCNSL and systemic lymphoma.
We investigated the role of CDKN2A deletion in urothelial carcinogenesis, as a function of FGFR3 mutation status, a marker for one of the two pathways of bladder tumour progression, the Ta pathway.
In addition, putative TSGs including FHIT, p16(INK4a), and p19(ARF) were selected for mutation screening to investigate their potential participation in NPC tumorigenesis.
In addition, loss of PTEN and oncogenic activation of RAS seem to occur in a reciprocal fashion, both of which could cooperate with CDKN2A loss in contribution to melanoma tumorigenesis.
Our data indicate that genetic variants in CDKN2A, and possibly nearby genes, may be associated with ESCC and several other tumours, further highlighting the importance of 9p21.3 genetic variants in carcinogenesis.
Detection of promoter hypermethylation of cancer-related genes may be useful for cancer diagnosis or the detection of recurrence. p16, an inhibitor of the cyclin D-dependent protein kinases, is a classical tumor suppressor gene, and its inactivation is closely associated with carcinogenesis. p16 hypermethylation could be detected in each stage, which is consistent with the finding that aberrant methylation of p16 is a very early event in carcinogenesis.
Expression of two viral oncogenes, E6 and E7, in epithelial stem cells is required to initiate and maintain cervical carcinogenesis and results in significant overexpression of the cellular p16INK4a protein.
CDKN2 is not deleted with high frequency in primary breast carcinomas, and the p16 gene does not play a role in breast carcinogenesis via this mechanism.
Silencing of the p16 gene by methylation of its promoter CpG island was suggested as a unique molecular mechanism in the carcinogenesis of PRC compared with MRC or PC.
No association was established between occurrence of genetic aberrations at 9p21 and tumor stage or grade, supporting previous suggestions that CDKN2A/ARF inactivation is an early event in bladder carcinogenesis.
To investigate the molecular mechanism of p16 gene inactivation in gastric carcinogenesis, we examined the methylation status of p16 in GC using methylation-specific PCR.
Genetic disruption of Cdkn2a(p19Arf) (hereafter Arf) alone predisposes mice to tumorigenesis, demonstrating that Arf is a tumour-suppressor gene in mice.
Abolition of p21(Cip1/Waf1) and p16(Ink4a) functions prevented oncogenically activated Ras from inducing growth arrest and was sufficient for limited anchorage-independent growth but not tumorigenesis.
HPV-16 integration could be directly related to tonsillar carcinogenesis initially in tonsillar crypts, followed by cell cycle aberration such as p16 overexpression related to the G1-S phase.
Oncogene Bmi-1 was shown to be a functional target of miR-218, and the main downstream targets signaling, P16(Ink4a) and P14(ARF), were activated in Hotair-suppressed tumorigenesis.
These results suggest that p16(INK4a) promoter hypermethylation is an early and frequent event in gastric carcinogenesis and may serve as a new prognostic biomarker for the risk of gastric cancers.
These results showed that functional deficiencies in metabolic pathways that protect cells from carcinogen induced DNA damage might be linked to aberrant promoter methylation of the CDKN2A and RARB genes during lung carcinogenesis.
In this aspect, the potential role of the CDKN2 gene at 9p21-p22 in ovarian carcinogenesis was assessed in an extended panel of ovarian tumors, 11 human ovarian carcinoma cell lines, and 1 cervical tumor cell line.