lunes, 10 de septiembre de 2012

Prognostic significance of promoter DNA meth... [Clin Cancer Res. 2012] - PubMed - NCBI

Prognostic significance of promoter DNA meth... [Clin Cancer Res. 2012] - PubMed - NCBI

Clin Cancer Res. 2012 Aug 28. [Epub ahead of print]

Prognostic significance of promoter DNA methylation in patients with childhood neuroblastoma.


Molecular Epidemiology, Children's Cancer Institute Australia for Medical Research.



To characterize the clinical significance of promoter methylation in a cohort of primary neuroblastoma tumors and investigate the association between DNA methylation and clinical outcome. Methods: A customized Illumina GoldenGate methylation assay was used to assess methylation status of 96 CpG sites within 48 candidate genes in primary neuroblastoma tumors obtained from 131 children diagnosed in Australia. Genes were selected based on previous reports of altered DNA methylation in embryonal cancers. Levels of DNA methylation were validated in a subset of 48 patient samples using combined bisulfite restriction analysis (CoBRA) and bisulfite sequencing. A Cox proportional hazards model was used to investigate the association between promoter hypermethylation and the risk of relapse/death within 5 years of diagnosis, while adjusting for known prognostic factors including MYCN amplification, age and stage at diagnosis.


Levels of promoter methylation of DNAJC15, NTRK1 and TNFRSF10D were higher in older patients at diagnosis (p<0 .01=".01" 30="30" 95="95" adjusting="adjusting" after="after" age="age" amplification="amplification" analysis="analysis" and="and" at="at" clinical="clinical" diagnosis.="diagnosis." die="die" displayed="displayed" dnajc15="dnajc15" factors="factors" folh1="folh1" for="for" genes="genes" higher="higher" hypermethylation="hypermethylation" in="in" independent="independent" known="known" least="least" levels="levels" likely="likely" methylation="methylation" more="more" moreover="moreover" multivariate="multivariate" mycn="mycn" myod1="myod1" ntrk1="ntrk1" observed="observed" of="of" or="or" outcome="outcome" over="over" p="p" patients="patients" poorer="poorer" predictors="predictors" prognostic="prognostic" pycard="pycard" relapse="relapse" remained="remained" significant="significant" stage="stage" status="status" thbs1="thbs1" times="times" to="to" two="two" were="were" while="while" with="with">


Our findings highlight the potential use of methylation profiling to identify additional prognostic markers and detect new therapeutic targets for selected patient subsets.


[PubMed - as supplied by publisher]

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