p14ARF promoter region methylation as a marker for gliomas diagnosis

He, Jun; Qiao, Juan; Zhu, Haiqing

doi:10.1007/s12032-010-9651-8

Cited by 10 publications

(12 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this example, repression of ARF is required for neurosphere self-renewal. Others have proposed that methylation in the promoter region of the ARF gene may be used as a biomarker for the diagnosis of gliomas [43]. Interestingly, in contrast with what happens in mouse embryonic fibroblasts, we found that JMJD3 does not primarily induce demethylation of the ARF gene during neurogenesis.…”

Section: Discussioncontrasting

confidence: 77%

p53 Interaction with JMJD3 Results in Its Nuclear Distribution during Mouse Neural Stem Cell Differentiation

et al. 2011

View full text Add to dashboard Cite

Conserved elements of apoptosis are also integral components of cellular differentiation. In this regard, p53 is involved in neurogenesis, being required for neurite outgrowth in primary neurons and for axonal regeneration in mice. Interestingly, demethylases regulate p53 activity and its interaction with co-activators by acting on non-histone proteins. In addition, the histone H3 lysine 27-specific demethylase JMJD3 induces ARF expression, thereby stabilizing p53 in mouse embryonic fibroblasts. We hypothesized that p53 interacts with key regulators of neurogenesis to redirect stem cells to differentiation, as an alternative to cell death. Specifically, we investigated the potential cross-talk between p53 and JMJD3 during mouse neural stem cell (NSC) differentiation. Our results demonstrated that JMJD3 mRNA and protein levels were increased early in mouse NSC differentiation, when JMJD3 activity was readily detected. Importantly, modulation of JMJD3 in NSCs resulted in changes of total p53 protein, coincident with increased ARF mRNA and protein expression. ChIP analysis revealed that JMJD3 was present at the promoter and exon 1 regions of ARF during neural differentiation, although without changes in H3K27me3. Immunoprecipitation assays demonstrated a direct interaction between p53 and JMJD3, independent of the C-terminal region of JMJD3, and modulation of p53 methylation by JMJD3-demethylase activity. Finally, transfection of mutant JMJD3 showed that the demethylase activity of JMJD3 was crucial in regulating p53 cellular distribution and function. In conclusion, JMJD3 induces p53 stabilization in mouse NSCs through ARF-dependent mechanisms, directly interacts with p53 and, importantly, causes nuclear accumulation of p53. This suggests that JMJD3 and p53 act in a common pathway during neurogenesis.

show abstract

Section: Discussioncontrasting

confidence: 77%

p53 Interaction with JMJD3 Results in Its Nuclear Distribution during Mouse Neural Stem Cell Differentiation

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Alterations that inactivate CDKN2A gene have always indicated a worse prognosis in cancers. 17,18 However, in this study p14 ARF expression appears to be the main marker of worse prognosis in vulvar cancer, despite the fact that p53 expression and HPV infection have been considered the most important markers so far. 5,7,[19][20][21][22] p14 ARF protein expression evaluated by immunohistochemistry was observed in 16.4 % of the samples examined, in contrast to another study, which found a 35.9 % positivity for p14 ARF using the same scoring method.…”

Section: Discussionmentioning

confidence: 56%

Prognostication of Vulvar Cancer Based on p14ARF Status: Molecular Assessment of Transcript and Protein

et al. 2012

View full text Add to dashboard Cite

p14ARF represents an important marker of poor prognosis in VSCC. p53 and HPV infection did not show any prognostic importance. Further clinical trials concerning p14ARF positivity may result in important contributions due to its relationship with poor outcome. Mainly due to the relationship of p14ARF with lymph node metastasis, the immunohistochemistry evaluation of this marker may help to identify a subset of patients more suitable to less radical procedures.

show abstract

“…When it comes to serum RASSF1A methylation-positive cases of brain tumor patients, similar results were obtained in the study of Dammann et al (2005). The second gene which also showed frequent hypermethylation in the studied patient group was p14ARF , and recent data suggest that methylation in the promoter region of p14ARF may be used as a biomarker for the diagnosis of gliomas (He et al 2011). We observed an intermediate frequency of MGMT methylation in the serum of patients with glial tumors (17.65 %), while it was low (6.25 %) in the serum of non-glial tumor patients.…”

Section: Discussionmentioning

confidence: 81%

Detection of MGMT, RASSF1A, p15INK4B, and p14ARF promoter methylation in circulating tumor-derived DNA of central nervous system cancer patients

et al. 2013

View full text Add to dashboard Cite

Despite the growing understanding of the mechanisms of carcinogenesis, cancers of the central nervous system are usually associated with unfavorable prognosis. The use of an appropriate molecular marker may improve the treatment outcome by allowing early diagnosis and treatment susceptibility monitoring. Since methylation of tumor-derived DNA can be detected in the serum of cancer patients, this makes DNA methylation-based biomarkers one of the most promising diagnostic strategies. In this study, the methylation profiles of MGMT, RASSF1A, p15INK4B, and p14ARF genes were evaluated in serum free-circulating DNA and the corresponding tumor tissue in a group of 33 primary or metastatic central nervous system cancer patients. Gene promoter methylation was assessed using methylation-specific polymerase chain reaction (PCR). All the tested genes were found to be methylated to a different extent in both serum and tumor samples. In comparison to metastatic brain tumor patients, the patients with glial tumors were characterized by a higher frequency of gene hypermethylation. The hypermethylation of RASSF1A differentiated primary from metastatic brain cancers. Moreover, the gene methylation profiles observed in serum, in most cases, matched the methylation profiles detected in paired tumor samples.

show abstract

p14ARF promoter region methylation as a marker for gliomas diagnosis

Cited by 10 publications

References 32 publications

p53 Interaction with JMJD3 Results in Its Nuclear Distribution during Mouse Neural Stem Cell Differentiation

p53 Interaction with JMJD3 Results in Its Nuclear Distribution during Mouse Neural Stem Cell Differentiation

Prognostication of Vulvar Cancer Based on p14ARF Status: Molecular Assessment of Transcript and Protein

Detection of MGMT, RASSF1A, p15INK4B, and p14ARF promoter methylation in circulating tumor-derived DNA of central nervous system cancer patients

Contact Info

Product

Resources

About