Title: Abstract LB-312: Methylated RASSF1a is the first specific DNA marker for minimal residual disease testing in neuroblastoma
Abstract: Abstract Purpose PCR-based detection of minimal residual disease (MRD) in neuroblastoma is presently based on neuroblastoma-specific transcripts. However, the expression of these targets varies between patients and upon treatment, and only PHOX2B is truly specific. RASSF1a is methylated (RASSF1aM) in neuroblastoma and we investigated whether it can serve as a specific and stable DNA MRD marker. Patients and methods The RASSF1aM specific real-time quantitative (RQ)-PCR was tested on control bone marrow (BM) (n=50), on 71 neuroblastoma tumors and on 159 clinical BM samples at diagnosis and at follow up of 77 patients. Results were compared to a panel of RNA markers and correlated with prognosis. Results RASSF1aM was present in all stage 4 and 4s tumors (n=50) and in 86% stage 1–3 tumors (n=21). The level of methylation in stage 4 neuroblastoma was correlated with overall survival (p=0.02). RASSF1aM-PCR was highly specific (only one amplification in 50 control samples tested in triplicate) and had a similar sensitivity as the RNA-based PCRs as shown on clinical samples. Moreover, RASSF1aM enabled accurate quantification without need for the original tumor. Conclusion RASSF1aM is a novel, highly specific DNA marker for MRD detection in neuroblastoma, equal to PHOX2B in specificity and sensitivity, and better suitable for MRD quantification. We propose to include RASSF1aM in further prospective MRD studies in neuroblastoma alongside RNA MRD markers. In addition, this assay can be used for sensitive detection and quantification of circulating cells in all cancers with hypermethylated RASSF1a. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-312. doi:10.1158/1538-7445.AM2011-LB-312
Publication Year: 2011
Publication Date: 2011-04-01
Language: en
Type: article
Indexed In: ['crossref']
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