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CDKN2A is methylated. 1000 / 5556
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"CDKN2A has been proved to bear a striking resemblance to classic TSGs such as p53 , and to be an important negative regulator of cell growth and proliferation. xref It is largely reported that a critical mechanism for silencing CDKN2A is hypermethylation of its regulatory region. xref Abnormal methylation of the CDKN2A gene is a common event in many types of human cancer, as well as in cervical cancer. xref , xref – xref However, conclusions regarding the role of methylated CDKN2A during the carcinogenesis of cervical cancer are inconsistent."
sparser
"Total DNA methylation and promoter-specific methylation of the two tumor suppressor genes, p14ARF and p15INK4b , were performed employing the DNA derived from 40 petrochemical employers subjected to ambient benzene concentrations of <1 ppm, and 31 office employers not subjected to benzene."
sparser
"Methylation of p16, MINT1, MINT2, MINT31, and hMLH1 was analyzed by methylation-specific polymerase chain reaction in 102 HPs, 8 serrated adenomas, 19 tubular adenomas, and 9 adenocarcinomas from 17 patients, with multiple/large HPs or hyperplastic polyposis and in 16 sporadic HPs from 14 additional patients."
sparser
"PTEN and CDKN2A methylation levels were low and increased in late stage III and IV (p = 0.003, p = 0.004 between stage I and III, p = 0.018 and p = 0.003 between stage I and IV), while MGMT methylation levels were low and appear to decrease with tumor stage (p = 4.5e-4 between stage I and IV) (Figure xref )."
sparser
"Without analysis of CIMP that is a potential confounder, some studies reported that CDKN2A methylation was significantly associated with worse prognosis in multivariate analysis; xref , xref however, those studies were limited by small sample sizes (N=90 and N=151, respectively)."
sparser
"Next, we evaluated the degree of p14 ARF promoter methylation, limiting the analysis to tumors and corresponding adjacent colon mucosa from 35 randomly selected patients (Table xref ), including one of the seven CRCs that was identified as having heavy methylation by MSP (sample T2, Table xref )."
sparser
"In a comparison of patients with and without adenomas, the methylation of p16 , MLH1 and MGMT could not predict the presence of adenoma ( xref ); in colorectal cancer patients, significant methylation was observed at the surgical margin (⩽10 cm from tumour) and was shown to be influenced by gender and by a polymorphism in the DNMT3B gene ( xref ; xref ; xref ; xref )."
sparser
"However, on the other hand, DNA methylation, methyltransferase I protein expression and p16 promoter methylation were significantly reduced in 14 FAP patients who received black raspberry powder for nine months by oral administration (1787 mg/individual/day) and rectal insertion (595 mg/individual/day) of two suppositories [ xref ]."
sparser
"A previous meta-analysis only reported that p16 methylation was significantly higher in HCC than in normal or adjacent tissues by Zhang et al, 2016.[ xref ]The present results compare favorably with the previous meta-analysis by Zang et al, 2011,[ xref ]which also reported that p16 promoter methylation was correlated with HCC risk in cancer versus liver cirrhosis."
sparser
"In conclusion, the methylation susceptibility of p16(ink4a) and p19(arf) to carcinogen treatments was remarkably different: X-radiation indirectly induces systemic p16(ink4a) methylation, especially in the intestine; whereas N-nitrosomethylurea and/or H. felis infection induce p19(arf) methylation in their target organs."
sparser
"An important study by Belinsky et al . reported aberrant promoter methylation of p16 , which was described to be commonly methylated in lung tumours, xref in at least one bronchial epithelial site from 44% of lung cancer patients examined. xref Moreover, p16 and death-associated protein kinase (DAPK) promoter methylation was observed frequently in bronchial epithelium from current and former smoker but not from never-smoker lung cancer patients and persisted after smoking cessation."
sparser
"Later, AAH lesions were shown to exhibit LOH of tuberous sclerosis complex (TSC)-associated regions, activation of telomerase, loss of LKB1 , overexpression of DICER, a key effector protein for small interfering RNA and miRNA function, and DNA methylation of CDKN2A and PTPRN2 . xref , xref , xref It is important to note that several studies have attempted to globally comprehend differential gene expression patterns and copy-number alterations between low-grade lesions (e.g. precursor lesions) or in situ adenocarcinomas and invasive tumours and found that amplification of the EGFR oncogene was the predominant differential molecular feature between the two different adenocarcinoma grade classes and occurred after mutations in the gene. xref Importantly, as will be discussed in the next section of this review, EGFR mutations also preceded changes in copy number of the gene when studying histologically normal bronchiolar epithelia. xref "
sparser
"As one pathway to obesity has been suggested to involve fetal undernutrition followed by rapid postnatal weight gain, we used longitudinal measurements of fetal growth from the SWS cohort to derive conditional abdominal growth velocity in late gestation and related this to cord CDKN2A methylation."
sparser
"Our results reinforced the notion that P16 methylation was a frequent and early event in ESCC development. xref We observed a significant increase in the P16 methylation frequency from no dysplasia to ESCC, which is at the same level as other findings. xref , xref Notably, we found that P16 methylation in cytology specimens was more sensitive than that in biopsy specimens for diagnosing ESCC and ESCdys, although the differences at each stage of ESCC development indicated no significant difference."
sparser
"The presence or absence of methylation of the p16INK4a gene did not correlate with clinical characteristics of the gastrinoma, biological behavior (gastrin release and basal or maximal acid output), the presence or absence of known prognostic factors (tumor size, gastrinoma location, lymph node metastases, liver metastases, and curability), or growth pattern of the gastrinoma postresection."
sparser
"More importantly, overexpression of the DNMT3a collaborates with PML–RARalpha to promote APL leukaemogenesis in vivo ( xref ), and aberrant DNA methylation in p15 and p16 genes has negative prognostic impact in APL patients ( xref ; xref ), suggesting a critical role of aberrant DNA methylation in APL pathogenesis."
sparser
"These results suggest that the aberrant p16INK4A RNA transcript can be transcribed from the methylated p16INK4A gene, and endogenous reactivation of functional p16INK4A mRNA by a demethylating agent can restore the pRB pathway in HCC, and foster the terminal differentiation of the malignant cells."
sparser
"Associations of p16 methylation with the following outcomes were observed: gastric oncogenesis (p < 0.00001); intestinal metaplasia (p = 0.002); poor histological differentiation (p = 0.03); local invasion (p = 0.001); lymph node dissemination (p = 0.03); more advanced TNM staging (p = 0.01); and Epstein Barr virus infection (p < 0.00001)."
sparser
"We analysed 64 primary lung carcinomas for promoter methylation of the tumour suppressor genes (TSGs) p16 (p16(INK4a)/CDKN2A) and p14 (p14(ARF)) by methylation-specific PCR, in order to evaluate aberrant methylation as a potential biomarker for epigenetic alterations in tobacco-related lung cancer."
sparser
"In the proximal colon cancer network, MSI was positively correlated with MLH1 methylation (correlation coefficient [ρ] = 0.77), CACNA1G methylation (ρ = 0.55), RUNX3 methylation (ρ = 0.50), SOCS1 methylation (ρ = 0.49), IGF2 methylation (ρ = 0.46), CRABP1 methylation (ρ = 0.45), BRAF mutation (ρ = 0.44), TIL (ρ = 0.41), NEUROG1 methylation (ρ = 0.37), Crohn’s-like reaction (ρ = 0.37), CDKN2A methylation (ρ = 0.33), abundance of Fusobacterium nucleatum (ρ = 0.33), SIRT1 overexpression (ρ = 0.25), loss of CDX2 expression (ρ = 0.25), CCND1 overexpression (ρ = 0.25), LINE-1 methylation (ρ = 0.24), peritumoral lymphocytic reaction (ρ = 0.24), MIR155 expression (ρ = 0.22), and intratumoral periglandular reaction (ρ = 0.22)."
sparser
"The results of a study from Japan have shown that alteration of the deleted in lung cancer 1 (DLC1) gene may be involved in development of ESCC. xref According to other studies, changes in the p16INK4a and p15INK4b genes have been found in 68% and 50% of ESCC patients, which suggests these changes are important in the pathogenesis of ESCC. xref Guo et al. have also found frequent methylation of the p16INK4a gene in ESCC patients. xref "
sparser
"We studied, by pyrosequencing, the methylation of tumor suppressor gene p16 , DNA repair genes MLH1 and MGMT , and the repetitive element LINE-1 (as a surrogate for global DNA methylation), in blood of elderly individuals ( n = 249) who had been exposed to folic acid (FA) through FA-fortified wheat flour during the last 12 years."
sparser
"Moreover, Pierini et al. described that traditional risk factors (tobacco and alcohol consumption) affect epigenetic modification of specific genes in laryngeal carcinomas, underlining the implication of CDKN2A and MLH1 promoter methylation in invasion of lymph nodes with cancer cells [ xref ]."
sparser
"A study analyzing promoter methylation of 15 candidate genes (Steinmann et al. xref ) in tumors and matched normal tissue from patients with HNSCC has shown that methylation of the p16 , MGMT , DAPK , RARβ , hMLH1 , CDH1 , RASSF2 , RASSF5 , and MST1 genes was significantly more frequent in the tumors than the normal tissue (Steinmann et al. xref )."
sparser
"One study reported the relationship between p14 methylation and clinical stage,[ xref ]but the other studies showed no association.[ xref , xref ] p14 methylation was negatively associated with GS by Verdoodt 2011 et al,[ xref ]while no correlation was reported among the remaining 4 studies.[ xref , xref , xref , xref ]The results demonstrated that p14 methylation was not linked to clinical stage and GS of patients with PCa."
sparser
"For example, analysis of RASSF1A, p16 INK4A and APC methylation in bronchial aspirates showed that cytology, quantitative MSP and histology could detect lung cancer in 44%, 53% and 59% of cases respectively, yet when combined diagnostic sensitivity extended to 81% (69/85) of patients xref ."
sparser
"In order to enable most DNA samples methylation-informative after adjustment of input DNA, we selected 1.6% as the cutoff proportion of methylated P16 to definite a P16 methylation-positive sample (the minimum required total DNA, 38 ng; 9.4 ng/MethyLight reaction, two reactions for methylated- P16 and two reactions for the COL2A1 reference)."
sparser
"We also observed that the levels of Cu, Pb, Se, Mn, and Ti decreased during the fifth day of exposure, and only lead, titanium and copper showed a low significant correlation with the methylation level mean for three specific CpG sites of the CDKN2A . Conclusions: In summary, the data suggest that altered levels of CDKN2A methylation in construction workers may be a potential biomarker of recent exposure in this environment."
sparser
"P14 methylation showed a higher frequency in PCa than in urine samples without cancer,[ xref ]but another study demonstrated a similar frequency in PCa and control urine samples without cancer.[ xref ]Our results showed that p14 methylation was not associated with PCa in the urine."
sparser
"Of the eligible studies, 17 studies evaluated the relationship between p16 methylation and PCa in cancer versus different control groups.[ xref – xref , xref , xref , xref , xref – xref ]12 studies including 748 patients with PCa assessed the correlation of p16 methylation with the clinicopathological characteristics of PCa.[ xref , xref , xref , xref , xref – xref , xref – xref , xref , xref ]Seven publications analyzed the correlation between p14 methylation and PCa.[ xref , xref , xref , xref , xref , xref , xref ]The basic characteristics of the eligible publications are listed in Table S1."
sparser
"PRMT6 can also interact with p16, overexpression of PRMT6 can counteract the cell cycle arrest at G1 phase caused by p16 in NSCLC A549 cells and decrease the association intensity of p16-CDK4, suggesting that PRMT6 probably achieves its cell apoptosis restraint role in NSCLC through p16 arginine methylation and provide a new idea for NSCLC treatment ( xref )."
sparser
"Tumor suppressor genesp16 INK4A ,p14 ARF , andp15 INK4B encoding cell-cycle regulatory proteins play a crucial role in the negative regulation of the cell cycle and the inhibition of the cell proliferation. xref The silencing ofp16 INK4A ,p14 ARF , andp15 INK4B genes by DNA methylation of the C-phosphate-G (CpG) islands of the promoter regions has been reported to be involved in the carcinogenesis and be an early biologic event in many cancers. xref – xref Based on a meta-analysis, Gu et al reported thatp16 INK4A promoter methylation may play a key role in the tumorigenesis of lung cancer. xref However, whetherp14 ARF orp15 INK4B promoter methylation plays a crucial role in the carcinogenesis of lung cancer, which remains to be certified."
sparser
"Several studies have investigated the effects ofp16 INK4a methylation in primary OSCC xref – xref and reported a range of 23 to 87% methylation, making methylation of this gene a very important component of marker panels for tumor screening and detection. xref – xref Our study showed methylatedp16 INK4a in 47.8% OSCCs."
sparser
"In these 49 GC cell lines, Epstein-Barr virus (EBV) and high microsatellite instability (MSI-H)-type cell lines were p16 methylated and sensitive to abemaciclib; further, genomically stable (GS), and chromosomal instability (CIN)-type cell lines with p16 methylation and intact Rb were also found to be responsive."
sparser
"Several studies have shown that promoter methylation of multiple tumour-related genes is present in gastric epithelial tissues with or without cancer, and that accumulations of such genes promote gastric carcinogenesis ( xref ; xref ; xref , xref , xref ; xref ; xref ; xref ). xref reported that among 94 samples obtained from patients with gastric cancer, promoter methylation of E-cadherin, hMLH1 , and p16 was found in 67, 24, and 44% of the surrounding gastric epithelial tissues, respectively. xref reported that among 268 samples obtained from gastric epithelial tissues without cancer, promoter methylation of DAP-kinase, E-cadherin, THBS1, TIMP3, p14, MGMT, p16, COX2, GSTP1 hMLH1, and RASSF1A was observed in 53.7, 41.0, 37.7, 23.1, 18.7, 10.9, 10.0, 4.1, 3.4, 1.7, and 0.4%, respectively."
sparser
"The strong association seen between p16 methylation in the bronchial epithelium and corresponding primary tumor substantiates that inactivation of this gene, although not transforming by itself, is likely permissive for the acquisition of additional genetic and epigenetic changes leading to lung cancer."
sparser
"Importantly, our data suggest that circulating cell-free methylated INK4A may complement AFP to improve the positivity in HCC; the positive rates are 45.5%, 74.2%, and 80.3% in the 66 HCC cases for AFP, INK4A methylation, and in combination, respectively, using LOD cut-offs of 200 μg/L for AFP [ xref ] and 5% for INK4A methylation [ xref ]."
sparser
"In this prospective series of resected, early-stage lung cancers, we did not
detect an association between recurrence-free survival and tumor promoter
methylation of CDKN2A , CDH13 , RASSF1 , and APC in addition to five other
genes on our panel ( MGMT, GSTP1, DAPK, WIF-1, and METH-2 )."
sparser
"The platform was once again tested with methylated p14ARF by discriminating partially and fully methylated epialleles among a high background of unmethylated DNA and displayed an estimated loading efficiency of 80%, up to 7× more than the previous device, developing a simple and low-cost system for rare DNA methylation quantification [ xref ]."
sparser
"A relatively high frequency of CpG promoter methylation (52%) was found only in hTERT, with low frequency of methylation (<15%) in p16INK4a , TIMP3 , RASFF1 , and RARB , and no methylation in FHIT and APC .[ xref ] Given the presence of promoter methylation of APC , RASSF1 , and RARB in cutaneous melanoma, these findings suggest that cutaneous and UM likely undergo different epigenetic changes."
sparser
"Two studies observed no methylation in tumor suppressor gene panels including E-cadherin , p16 , p14ARF , APC and RASSF1A in urine DNAs from normal healthy individuals. xref , xref We have found a significant relation between smoking status of patients and controls regarding the methylation of CDH1 and p14ARF ."
sparser
"MSI, CIMP, LINE-1 methylation, and related molecular events such as BRAF mutation, are important potential confounders, because these molecular features have been associated with prognosis in large-scale studies. xref , xref , xref , xref Our current study is the only one study that assessed the prognostic significance of CDKN2A methylation and loss of CDKN2A (p16) independent of these potential confounders."
sparser
"For instance, CRC cells in which the cell cycle regulator p16 is methylated show considerable resistance to irinotecan [ xref ], as well as the hypermethylation of particular genes, such as SAT, C8orf4, LAMB3, is responsible for the decrease in sensitivity to cisplatin [ xref ]."
sparser
"Eads et al. reported the distribution of “fields” of methylation of CDKN2A, APC and ESR1 in esophagectomy specimens of BE resected for EA. xref ESR1 methylation was found in inflammatory reflux esophagitis and all subsequent stages whereas APC and CDKN2A methylation were found in BE metaplasia, dysplasia and carcinoma."
sparser
"Although no significant correlation between p14 ARF methylation and TP53 mutational status was seen ( P = 0.23), methylation involving the proximal CpG sites within the 5′ CpG flanking exon 1β was present more frequently in tumors with restricted p53 overexpression than in those with diffuse p53 overexpression (range of methylated clones 17 to 36% (95% CI 24 to 36%) versus range 0 to 3% (95% CI 0 to 3%), P = 0."
sparser
"The results of an analysis in which confounding factors were adjusted revealed that carrying the rs755622 C allele and the rs5844572 7-repeat allele was significantly associated with an increased methylation of both p14 ARF and p16 INK4a (OR, 2.70; 95% CI, 1.22–6.01; p = 0.015 and OR, 2.87; 95% CI, 1.25–6.62; p = 0.013, respectively; Table xref )."
sparser
"One study reported the relationship between p14 methylation and clinical stage,[ xref ]but the other studies showed no association.[ xref , xref ] p14 methylation was negatively associated with GS by Verdoodt 2011 et al,[ xref ]while no correlation was reported among the remaining 4 studies.[ xref , xref , xref , xref ]The results demonstrated that p14 methylation was not linked to clinical stage and GS of patients with PCa."
sparser
"Recent evidence suggests that environmental chemicals may cause diseases via epigenetic mechanisms that regulate gene expression without changing DNA sequencing, such as DNA methylation (i.e., cytosine modification at CpG dinucleotides), the most well-studied epigenetic mechanism in the etiology of disease. [ xref , xref ] Although most studies have been conducted using tissue samples, [ xref , xref ] evidence for As exposure and DNA methylation in blood DNA has also begun to accumulate. [ xref – xref ] A global dose-dependent hypermethylation of blood DNA was observed in a Bangladeshi population with chronic As exposure to contaminated drinking water. [ xref ] In a cross-sectional study of Indian individuals, As levels in contaminated water was also associated with global DNA hypermethylation in blood mononuclear cells. [ xref ] Chanda et al. observed blood DNA hypermethylation in the promoter of p53 and p16 in As-exposed Indian individuals. [ xref ] Consistently, in a Chinese population, increased DNA methylation in the p16 promoter was observed in arseniasis patients compared with people without a history of As exposure. [ xref ] However, these previous studies have been limited to the evaluation of global methylation markers or methylation alterations in a small group of genes."
sparser
"CDKN2A promoter methylation and loss of CDKN2A (p16) were associated with shorter overall survival in univariate Cox regression analysis [hazard ratio (HR), 1.36; 95% CI, 1.10-1.66; p=0.0036 for CDKN2A methylation; HR, 1.30; 95% CI, 1.03-1.63; p=0.026 for CDKN2A (p16) loss] but not in multivariate analysis that adjusted for clinical and tumor variables including CIMP, MSI, and LINE-1 methylation."
sparser
"According to results from the above minimum TAIT for GFRA1 and P16 methylation analyses, when the cutoff value for the proportion of methylated GFRA1 or P16 alleles in a tested sample is set at 1.6%, in order to avoid false negative results, at least 9.4 ng bisulfite-treated input DNA (Ct COL2A1 ≤ 29.3) should be added into each PCR reaction."
sparser
"For example, Nadia et al. [ xref ] found a significant association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and p16 and O6-methylguanine-DNA methyltransferase (MGMT) gene promoter methylation in oral squamous cell cancer (OSCC) patients, which suggests that hypermethylation of cancer-related genes may be affected by MTHFR polymorphisms."
sparser
"There are available reports which have shown the effect of p16 methylation in precancerous oral lesions with and without epithelial dysplasia [ xref , xref ] and its association with advanced OSCC [ xref , xref – xref ]. von Zeidler et al. evaluated methylation status of p16 gene in premalignant oral lesions and found 9.7% of cases with promoter hypermethylation [ xref ]."
sparser
"MGMT was methylated in the circulating tumor-derived DNA from only one meningioma patient, RASSF1A methylation was found in two meningiomas and three metastatic tumors, and the methylation of both p15INK4B and p14ARF was detected in one meningioma and three metastatic tumors, respectively."
sparser
"As shown in xref , when the highest value of methylation of the seven CpG sites was used for each of the samples, there were significantly higher levels of INK4A methylation in HCC samples than in the benign liver disease samples (odds ratio=1.38 with 95% confidence interval of 1.05–1.79; p<0.05, Wald test)."
sparser
"In case-case comparisons of premenopausal breast cancer, lower birth weight was associated with increased likelihood of E - cadherin promoter methylation (OR = 2.79, 95% CI, 1.15–6.82, for ≤ 2.5 vs 2.6–2.9 kg); higher adult height withRAR-β 2 methylation (OR =3.34, 95% CI, 1.19–9.39, for ≥ 1.65 vs <1.60 m); and not having been breast fed with p16 methylation (OR = 2.75, 95% CI, 1.14–6.62)."
sparser
"The methylation-specific PCR (MSP) was used to study methylation of the p16, retinoic acid receptor-beta (RARbeta), death-associated protein (DAP) kinase, and O(6)-methylguanine-DNA-methyltransferase (MGMT) genes in 75 NSCLCs [44 adenocarcinomas and 31 squamous cell carcinomas (SCCs)] and 68 BALs from suspected lung cancers."
sparser
"While the p16 gene methylation has been reported as one of the earliest methylation events in lung cancer development, occurring in the bronchial epithelium of some current and former smokers [ xref ], we did not find methylation in pretested exhaled samples, nor in the lung cancer cell line A549 cells (not shown)."
sparser
"We studied the HLA association, aberration p15, p16 and p73 promoter methylation and microsatellite instability in Chinese primary thyroid lymphoma patients to elucidate their relationship with AITD and the relationship between thyroid diffuse large cell lymphoma (DLCL) and marginal zone lymphomas (MZL)."
sparser
"Our biomarker qualification process through training and validation sets demonstrated that a panel of TERT, WT1, p16 and RASSF1 methylation markers provides a parsimonious and efficient algorithm for correctly predicting lung cancer status in 85.9% of tested bronchial washing specimens."
sparser
"Although Wong et al xref reported that p16 promoter methylation was associated with advanced stage and poorer survival of endometrial cancer, no correlation was observed between promoter methylation of p16 and clinicpathological features and prognosis of endometrial cancer in another recent study xref ."
sparser
"However, we did not observe considerable differences in key socio-demographic and clinicopathological features between BC patients with and without available tissue or blood data. xref , xref Second, the low prevalence of some methylation biomarkers (i.e., low frequency of CDKN2A and CDH1 methylation) in our study sample, as reflected in the wide confidence intervals, may have contributed to our inability to detect modest interactions; thus, these results should be interpreted with caution."
sparser
"With our large dataset, we could examine the prognostic effect of CDKN2A methylation independent of CIMP status [i.e., multivariate analysis summarizing CDKN2A -methylated (N=121) vs. unmethylated (N=20) in CIMP-high tumors and CDKN2A -methylated (N=148) vs. unmethylated (N=613) in non-CIMP-high tumors, adjusted for other variables]."
sparser
"These results suggest that aberrant p14ARF expression due to homozygous deletion or promoter hypermethylation is associated with the evolution of both primary and secondary glioblastomas, and that p14ARF promoter methylation is an early event in subset of astrocytomas that undergo malignant progression to secondary glioblastoma."
sparser
"Cluster analysis separated tumours based on single-gene driver events as well as large-scale aberrations, emphasizing lung adenocarcinoma’s molecular heterogeneity and combinatorial alterations, including the identification of coincident SETD2 mutations and CDKN2A methylation in a subset of CIMP-H tumours, providing evidence of a somatic event associated with a genome-wide methylation phenotype."
sparser
"The expression of DeltaDNMT3B variants was associated with p16 and RASSF1A promoter methylation in the tumors, but the strongest association was between DeltaDNMT3B4 and RASSF1A. Forty-two of 46 (91%) tumors with RASSF1A promoter methylation expressed DeltaDNMT3B4 compared with only 13 of 73 (18%) tumors without the promoter methylation (P < 0.0001)."
sparser
"The reported rate of incidence of p16INK4A methylation in HCC is quite variable, ranging from 0 to 94%[ xref xref xref ] and from 29.4 to 83% in cirrhosis.[ xref xref xref ] Wong et al .,[ xref ] reported that p16INK4A methylation was neither detected in the plasma of patients with LC nor hepatitis."
sparser
"According to this analysis above, HCC pathogenesis associated with p16 methylation risk did not work during normal person, its role started from benign liver disease, while developing HCC, patients in HCC increased risk quickly, HCC pathogenesis had dramatically a powerful role."
sparser
"Finally, in 2013, Dang et al. ( xref ) studied the epigenetic changes in the promoter of microRNA-137 in 20 OLP tissue samples, 12 OSCC and 10 controls and observed methylation in both microRNA-137 and p16 protein in OLP patients although at a lesser extent than in OSCC patients."
sparser
"Previous studies have revealed that promoter methylation of BRCA1 and RASSF1A is linked to a poor prognosis of breast cancer patients in OS and DFS.[ xref , xref ]There were some inconsistent and conflicting results on multivariate regression analysis of GSTP1 , p16 , ESR1, or PITX2 promoter methylation for the prognosis of breast cancer."
sparser
"p14 methylation has been comparatively less studied but has been shown to be hypermethylated in approximately 57% (34/60 samples) of melanoma samples, independently of the p16 promoter (88% of the time), but also in conjunction with p16 promoter methylation (12% of the time) [ xref ], findings that were later corroborated by additional studies [ xref ]."
sparser
"Consequently, we were unable to assess the dependence on cellular heterogeneity of the association of CDKN2A methylation in blood and BMI, and therefore cannot exclude differences in cellular composition as the explanation for the association between CDKN2A methylation in peripheral blood and adiposity in late adolescence."
sparser
"Aberrant p16 methylation was detected in both hepatocellular carcinoma tissues and plasma/serum samples by xref two decades ago. xref found that the methylation status of γ-glutamyl transferase gene altered and γ-glutamyl transferase expressed abnormally in hepatocellular carcinoma. xref identified around 3,700 hypomethylated promotors in liver cancer samples."
sparser
"In the multivariate analysis, the poor prognosis associated with concurrent methylation in NEUROG1 and CDKN2A (p16) in male was independent of other clinico-pathologic prognostic factors (adjusted HR for OS 5.23, 95 % CI 2.45–11.17, p < 0.001) (adjusted HR for DFS 3.66, 95 % CI 1.82–7.36, p < 0.001) (Table xref )."
sparser
"The results from bronchial aspirates showed that a significant correlation was observed between the methylation of the P16 (OR = 8.15, 95% CI = 3.18 - 20.87, P < 0.001), RASSF1A (OR = 32.60, 95% CI = 19.21 - 55.32, P < 0.001), APC (OR = 11.88, 95% CI = 4.75 - 29.72, P < 0.001) and SHOX2 (OR = 50.10, 95% CI = 30.30 - 82.84, P < 0.001) genes with lung cancer in more than four studies, including 840 lung cancer patients and 800 controls (Figure xref ), 980 lung cancer patients and 733 controls (Figure xref ), 360 patients with lung cancer and 273 controls (Figure xref ), and 493 patients with lung cancer and 415 controls (Figure xref ), respectively."
sparser
"Therefore, the researchers have concluded that ΔNp63 is a good and highly specific blood marker for early detection of ESCC. xref Hibi et al. found a high rate of promoter methylation of the p16 gene in the serum of ESCC patients, which suggested that p16 gene promoter methylation may be used as a serum marker for identifying precursor lesions of ESCC. xref "
sparser
"Since the four CpG loci associated with CDKN2A were not present in the Illumina platform used to generate TCGA data sets, we confirmed the association between methylation of the downstream region of CDKN2A and HPV status by using an alternate CpG locus in the same CDKN2A downstream region not present in our panel but found in the TCGA data set (Table xref )."
sparser
"Even though a high frequency of p14 ARF promoter methylation has been previously reported to occur in tumors without TP53 mutations [ xref , xref , xref , xref ], an inverse correlation between TP53 mutations and epigenetic inactivation of p14 ARF in CRCs does not always hold true [ xref ]."
sparser
"To assess the associations ofP16 INK4a methylation status with low-grade squamous intra-epithelial lesion (LSIL), high-grade squamous intra-epithelial lesion (HSIL), cervical cancer (CC) and their clinicopathological features, a meta-analysis with 29 eligible studies was conducted."
sparser
"Methylation of various genes, including retinoic acid receptor 2 beta ( RAR-b2 ), H-cadherin , APC , p16 and RASSFF1A was described in bronchial epithelial cells of heavy smokers. xref Moreover, methylation of p16 , GSTP1 and DAPK was reported to be evident in bronchial brushings of one third of the cancer-free smokers examined. xref In the same study by Belinsky et al ., as mentioned before, methylation of p16 was detected in epithelia of cancer-free smokers. xref A more detailed list of aberrant gene promoter methylation in lung cancer patients and cancer-free smokers is nicely summarized and explained in the review by Heller et al . xref "
sparser
"Our results suggest that inactivation of the RB1 pathway may play a causal role in pituitary tumorigenesis, with hypermethylation of the p16(INK4a) gene being the most common deregulation, and further provide evidence that RB1 and p16(INK4a) methylations tend to be mutually exclusive but occasionally coincide with p15(INK4b) methylation."
sparser
"No statistically significant differences in total surface area of the Barrett's esophagus; in prostaglandin levels; in cyclooxygenase-1/2 mRNA levels; or in methylation of tumor suppressor genes p16, adenomatous polyposis coli, and E-cadherin were found with celecoxib compared with placebo."
sparser
"Epigenetic modifications such as increased promoter hypermethylation of genes implicated in lung cancer (e.g., p16 ) with histologic progression from normal to AAH and finally LUAD [ xref ], as well as DNA methylation of CDKN2A and PTPRN2, have also been reported in AAHs [ xref ]."
sparser
"Methylatedp16 INK4A was significantly associated with tumor size, in which it was higher in pT2-4 patients than in pT1 patients, suggesting thatp16 INK4A promoter methylation may play a key role in the pathogenesis of T2-4, whereas methylatedp14 ARF was not significantly correlated with tumor size."
sparser
"DNA methylation of 2 genes, VHL and CDKN2A , were especially analyzed in the 16 RCCs arising in ESRD because they are known to be epigenetically silenced in small subsets of sporadic ccRCCs ( VHL , 7%‐10%), xref , xref , xref , xref PRCCs ( CDKN2A , 6.2%) xref and ChRCCs ( CDKN2A , 6.1%). xref However, we did not find either VHL or CDKN2A methylation in ESRD‐ccRCCs or ACD‐associated RCCs (Table xref )."
sparser
"Further, CDKN2A promoter methylation is observed in rat lung tumors induced by exposure to various mutagenic agents (X-rays, plutonium-239 oxide, beryllium metal, cigarette smoke) indicating that the methylation induction can occur in response to different types of environmental insults."
sparser
"Betel quid and tobacco chewing habit synergistically with p16 methylation elevated the risk for esophageal cancer development (adjusted odds ratio (OR) = 6.88, 95% confidence interval (CI) = 1.64-28.81, p = 0.003 for betel quid chewing and adjusted OR = 7.02, 95% CI = 1.87-26.38, p = 0.001 for tobacco chewing)."
sparser
"The methylation status of five genes- CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS126 may identify CpG island methylator phenotype (CIMP) positive colon cancers, which are characterized by high incidence of p16 and THBS1 methylation and frequent KRAS and BRAF mutations ( xref ; xref )."
sparser
"Varying degrees of p16 methylation has been reported in OSCC (Ohta et al. xref ; Ruesga et al. xref ; Nakahara et al. xref ; Huang et al. xref ; Yakushiji et al. xref ; Nakahara et al. xref ; Miracca et al. xref ; Riese et al. xref ; El-Naggar et al. xref ; Tao et al. xref ; González et al. xref ; Reed et al. xref ), in mucoepidermoid carcinoma (MEC) of the salivary glands (Guo et al. xref ; Agnese et al. xref ), in HNC (Yalniz et al. xref ; Koscielny et al. xref ; Ai et al. xref ), and in larynx cancer (Smigiel et al. xref )."
sparser
"Our major findings are a) methylation status of any single gene was largely independent of methylation status of other genes; b) the rates of methylation of p16 and APC and the mean Methylation Index (MI), a reflection of the overall methylation status, were significantly higher in ever smokers than in never smokers; c) the mean MI of tumors arising in former smokers was significantly lower than the mean of current smokers; d) the methylation rates of APC, CDH13 and RARbeta were significantly higher in adenocarcinomas than in squamous cell carcinomas; e) methylation rates of MGMT and GSTP1 were significantly higher in the USA and Australian cases than in those from Japan and Taiwan; and (f) no significant gender-related differences in methylation patterns were noted."
sparser
"As shown in Figure xref , we found a statistical difference between HCC tumor tissues and adjacent tissues for p16 methylation in China from 28 studies (OR = 4.88, 95% CI = 3.50–6.81, I 2 = 66%, p < 0.00001) and in Japan from 6 studies (OR = 8.43, 95% CI = 3.71–19.19, I 2 = 68%, p < 0.00001), but not in Germany from 3 studies ( p = 0.12, I 2 = 86%)."
sparser
"After sex, season, SO 2 level, temperature, and age were adjusted, the results showed that every 1 μg/m 3 increase of PM 2.5 resulted in 0.04% increase of p16 CDKN2A promoter methylation in blood DNA, 0.02% and 0.06% decrease of LINE - 1 and iNOS methylation in lung tissue DNA, 0.01% and 0.01% increase of APC and p16 CDKN2A promoter methylation in lung tissue DNA, and 0.64 and 0.66 ng/mg protein increase of H3K9ac from PBMC and lung tissue histone, respectively."
sparser
"However, these results were only seen in certain subsets of patients (older or younger) in this small study and were not confirmed with multivariate analysis.( xref ) In another report of 78 cases with oral epithelial dysplasia, the rate of progression to oral cancer in lesions with p16 methylation was significantly higher than when p16 was not methylated."
sparser
"A number of nested case-control studies and followup cohorts consistently showed p16 methylation as a potential biomarker for the early prediction of malignant transformation of epithelial dysplasia, one kind of precancerous lesion in many organs/tissues including the oral/oesophageal/gastric mucosa [ xref - xref ]."
sparser
"No correlation of p14 methylation was found in the tissue (cancer vs adjacent tissues)[ xref , xref ]and (cancer vs benign tissues).[ xref , xref ]The current results indicated no relationship between p14 methylation and PCa in tissue samples, which were consistent with an individual study."
sparser
"Our results show that the abnormal methylation of CDKN2A is significantly higher in cervical cancer than in control tissues (including both normal individual tissues and benign tissues), as well as in precancerous lesions (including CIN1–CIN3), and that the frequency of CDKN2A methylation is higher in CINs than in control tissues."
sparser
"Animal and epidemiological studies implicate EDCs as a significant concern to public health.( xref ) EDCs can interfere with the endocrine system, resulting in adverse health outcomes.( xref ) Many animal studies have linked EDCs such as diethylstilbestrol (DES), polychlorinated biphenyl (PCBs) and DDT exposure to epigenetic modifications including DNA methylation changes, resulting in alteration in gene expression and chromosomal stability.( xref – xref ) In particular, the mouse model had clearly established the ability of environmental factors to influence epigenetics thus promoting phenotypic changes later in development.( xref , xref ) Compared with controls, young rats exposed to DDT had lower methylation overall.( xref ) Rats treated in utero and postnatally with organochlorine pesticides and PCBs also showed decreased methylation in the tumor suppressor gene p16 (INK4a) compared to controls.( xref ) An in vitro study of rat ovarian cells observed that o , p’ -DDT can suppress the expression of selected genes (such as cytochrome P450 side chain cleavage enzyme (P450scc), progesterone receptor (PR), and epidermal growth factor epiregulin (EREG)) in very low doses through an estrogen receptor-independent pathway.( xref )"
sparser
"Due to the catalytic nature of the process, LOD of 7.3 × 10 −17 M was reached; moreover, biosensor could recognize as low as 0.01% methylation level, and was applied to analyze DNA methylation of p16 gene in various cancer cell lines, such as hepatoma cell line (Hep G2), breast cancer cell lines (MDA-MB-231 and MCF-7), cervical carcinoma cell line (HeLa), human lung adenocarcinoma cell line (A549), and normal human epithelial mammary cell line (MCF-10A)."
| PMC
sparser
"Our main findings are as follows: (a) methylation was completely absent in control tissues; (b) the frequencies of methylation for all of the genes except hMLH1 were >20% in cervical cancers; (c) aberrant methylation commenced early during multistage pathogenesis and methylation of at least one gene was noted in 30% of the nondysplasia/low-grade CIN group; (d) an increasing trend for methylation was seen with increasing pathological change; (e) methylation of RARbeta and GSTP1 were early events, p16 and MGMT methylation were intermediate events, and FHIT methylation was a late, tumor-associated event; and (f) methylation occurred independently of other risk factors including papillomavirus infection, smoking history, or hormone use."
sparser
"This study was designed to determine the prevalence of p16, MGMT, RARbeta2, CLDN3, CRBP and MT1G gene methylation in patients with ESCC to evaluate the variation of gene methylation across a spectrum of preneoplastic lesions, and assess the feasibility of using gene methylation in a primary screening test utilizing frozen esophageal cells collected by balloon cytology samplers."
sparser
"These findings showed methylation of the p16 gene was a frequent event inMM patients at diagnosis, and was associated with an increased proliferative rate of plasma cells and a poor prognosis, indicating an important role for p16 gene in the cell cycle regulation of multiple myeloma tumour cells, and thus in the clinical outcome of the disease."
sparser
"Moreover, these molecular aberrations were also found in carcinomas in situ and SCC, and at a more advanced level. xref Molecular changes involving LOH of chromosomal regions 3p ( DDUT and FHIT genes), 9p ( CDKN2A ), genomic instability (increased microsatellite repeats) and p16 methylation have all shown to commence in histologically normal or slightly abnormal tissue in SCC patients and in the sequence of pathogenesis of the disease. xref As mentioned before, KRAS is the most mutated oncogene in lung adenocarcinomas. xref Almost 15 years ago, Nelson et al . demonstrated that KRAS mutations are found in histologically normal lung tissue adjacent to lung tumours. xref As will be discussed later, mutations in EGFR were also found in adjacent to tumour histologically normal epithelium. xref , xref Similar epigenetic and gene methylation patterns between tumours and adjacent histologically normal epithelia were described."
sparser
"According to sample type (tissue, serum, or urine), ethnicity (Caucasian or Asian), and testing method [methylation-specific polymerase chain reaction (MSP) and non-MSP], subgroup analyses were performed forp16 INK4A promoter methylation with significant heterogeneity (Table xref )."
sparser
"Although the role of P16 methylation in ESCC development has been studied intensively, only one previous study examined P16 methylation in cytology specimens and reported that P16 methylation was observed in 9% subjects with no dysplasia, 8% with LGIN, 14% with HGIN. xref In contrast, our study showed a considerably higher sensitivity for identifying ESCdys and an increasing trend for P16 methylation frequency with pathological progression, which is consistent with other studies using biopsy specimen. xref , xref Differences in sampling devices or methylation detection technology may account for the better results in our study."
sparser
"In our study, we investigated promoter methylation of CDKN2A using a novel sensitive method, MethyLight assay, in addition to the standard method of MSP, and p16 expression to identify and differentiate HCC from non-HCC liver tumors in a series of patients presenting with a liver mass."
sparser
"To further evaluate the role of DNA methylation changes in fibrosis-associated mouse liver carcinogenesis, promoter methylation and expression of Cdkn2a , Mgmt , Socs1 , Cdh1 , and Riz1 in non-tumor liver tissue were examined. xref shows that these tumor suppressor genes were methylated in the non-tumorous liver samples in DEN+CCl 4 -treated mice, while they were largely unmethylated in the livers of control mice."
sparser
"Similarly, black raspberry anthocyanins when administered locally as a black raspberry rectal suppository significantly decreased cellular proliferation, DNA methylation methyl transferase 1 protein expression, and p16 promoter methylation in patients with familial adenomatous rectal polyps after a nine month intervention."
sparser
"In the present investigation, we have studied the role of p16 promoter methylation in 69 histopathologically confirmed ESCC tissues and compared it with corresponding normal adjacent tissues for DNA methylation in the CpG island in the p16 promoter region by methylation-specific polymerase chain reaction (MSP) and p16 protein expression by immunoblotting."
sparser
"The subgroup analysis by ethnicity regarding the methylation of P16 , RASSF1A , APC , and RARβ genes showed that the methylation of the P16 and RARβ genes was associated with the occurrence of NSCLC in the Asian and Caucasian populations with, suggesting that the methylation of P16 and RARβ genes can be used as biomarkers for NSCLC detection in both ethnical groups."