2006
DOI: 10.1186/1471-2407-6-254
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Frequent promoter hypermethylation of RASSF1A and CASP8 in neuroblastoma

Abstract: BackgroundEpigenetic alterations and loss of heterozygosity are mechanisms of tumor suppressor gene inactivation. A new carcinogenic pathway, targeting the RAS effectors has recently been documented. RASSF1A, on 3p21.3, and NORE1A, on 1q32.1, are among the most important, representative RAS effectors.MethodsWe screened the 3p21 locus for the loss of heterozygosity and the hypermethylation status of RASSF1A, NORE1A and BLU (the latter located at 3p21.3) in 41 neuroblastic tumors. The statistical relationship of… Show more

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Cited by 53 publications
(49 citation statements)
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“…Our results show that promoter hypermethylation of RASSF1A occurs at a high frequency in primary neuroblastoma tumours and no correlation between RASSF1A methylation and known prognostic factors including stage, age and MYCN amplification, or outcome was seen. The high proportion of RASSF1A promoter methylation in tumours agrees with earlier reports in the literature, which have found RASSF1A to be hypermethylated in 52 -94% of tumour DNA samples (Astuti et al, 2001;Harada et al, 2002;Wong et al, 2004;Yang et al, 2004Yang et al, , 2007Banelli et al, 2005;Lazcoz et al, 2006;Michalowski et al, 2008). Several earlier studies with one exception (Yang et al, 2004) failed to find a statistical correlation between RASSF1A methylation in tumours and poor outcome (Astuti et al, 2001;Harada et al, 2002;Banelli et al, 2005;Michalowski et al, 2008).…”
Section: Discussionsupporting
confidence: 81%
See 1 more Smart Citation
“…Our results show that promoter hypermethylation of RASSF1A occurs at a high frequency in primary neuroblastoma tumours and no correlation between RASSF1A methylation and known prognostic factors including stage, age and MYCN amplification, or outcome was seen. The high proportion of RASSF1A promoter methylation in tumours agrees with earlier reports in the literature, which have found RASSF1A to be hypermethylated in 52 -94% of tumour DNA samples (Astuti et al, 2001;Harada et al, 2002;Wong et al, 2004;Yang et al, 2004Yang et al, , 2007Banelli et al, 2005;Lazcoz et al, 2006;Michalowski et al, 2008). Several earlier studies with one exception (Yang et al, 2004) failed to find a statistical correlation between RASSF1A methylation in tumours and poor outcome (Astuti et al, 2001;Harada et al, 2002;Banelli et al, 2005;Michalowski et al, 2008).…”
Section: Discussionsupporting
confidence: 81%
“…RASSF1A falls into the category of genes frequently inactivated by methylation rather than mutational events. This gene is silenced and inactivated by promoter region hypermethylation in many adult and childhood cancers, including neuroblastoma (Astuti et al, 2001;Harada et al, 2002;Wong et al, 2004;Yang et al, 2004;Banelli et al, 2005;Lazcoz et al, 2006;Michalowski et al, 2008). RASSF1A has been shown to play important roles in cell cycle regulation, apoptosis and microtubule stability as a tumour suppressor gene (Agathanggelou et al, 2005).…”
mentioning
confidence: 99%
“…This pattern has also been seen in other studies, for example of CASP8 and RASSF1A (Lazcoz et al, 2006). No consistent CpG methylation sites in both NB cell lines and primary tumours differing from those of control blood DNA could be identified.…”
Section: Discussionsupporting
confidence: 57%
“…However, associations between RASSF1 methylation and clinical outcome of neuroblastoma have been variable. One study found significant association between RASSF1 methylation and high-risk neuroblastoma as well as poor survival (Yang et al, 2004), while other studies were unable to detect any associations (Harada et al, 2002;Wong et al, 2004;Lazcoz et al, 2006). Nevertheless, when the combined methylation levels of both RASSF1 and TNFRSF10D are considered, their clinical association with reduced overall survival and progressive tumors becomes more apparent (Banelli et al, 2005b).…”
Section: Tumor Suppressor Genesmentioning
confidence: 99%
“…Nevertheless, when the combined methylation levels of both RASSF1 and TNFRSF10D are considered, their clinical association with reduced overall survival and progressive tumors becomes more apparent (Banelli et al, 2005b). Similarly, methylation patterns in RASSF1 and CASP8 have been reported to be correlated, although the clinical significance of this association is yet to be established (Astuti et al, 2001;Lazcoz et al, 2006). More recently, a study examining the level of promoter hypermethylation of RASSF1 in serum DNA samples of patients with neuroblastoma found increased levels of RASSF1 hypermethylation associated with older age, stage 4 disease, and MYCN amplification (Misawa et al, 2009).…”
Section: Tumor Suppressor Genesmentioning
confidence: 99%