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Wimmer K Zhu XX Lamb BJ Kuick R Ambros P Kovar H Thoraval D Elkahloun A Meltzer P Hanash SM 《Medical and pediatric oncology》2001,36(1):75-79
BACKGROUND: Amplification of the oncogene MYCN in neuroblastoma has been found to correlate with aggressive tumour growth and is used as a predictor of clinical outcome. The MYCN amplicon is known to involve coamplification of extensive DNA regions. Therefore it is possible that other genes are coamplified in this amplicon and that they may play a role in the poor outcome of MYCN amplified tumours. PROCEDURE: We have implemented an approach for the two-dimensional separation of human genomic restriction fragments to detect and isolate as yet unknown amplified sequences in the MYCN amplicon in neuroblastoma. Using this approach we have recently cloned a novel gene referred to as NAG that is frequently coamplified with MYCN in neuroblastoma. RESULTS AND CONCLUSIONS: We report here the identification and cloning of two additional CpG islands that are amplified in neuroblastoma. One contains a sequence that is identical to the first intron of DDX1. The other represents a novel CpG island that is associated with an as yet unidentified gene. We show that the novel CpG island is located in close proximity to the MYCN locus on chromosome 2 and is as frequently coamplified with MYCN in neuroblastoma as NAG and DDX1. 相似文献
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Neurofibromin 1 (NF1) Defects Are Common in Human Ovarian Serous Carcinomas and Co-occur with TP53 Mutations
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Didier Thoraval Jun-ichi Asakawa Katharina Wimmer Rork Kuick Barbara Lamb Bruce Richardson Peter Ambros Thomas Glover Samir Hanash 《Genes, chromosomes & cancer》1996,17(4):234-244
Altered genomic methylcytosine content has been described for a number of tumor types, including neuroblastoma. However, it remains to be determined for different tumor types whether specific loci or chromosomal regions are affected by a methylation change or whether the change is random. We have implemented a computer-based approach for the analysis of two-dimensional separations of human genomic restriction fragments. Through the use of methylation-sensitive restriction enzymes, methylation differences in genomic DNA between tumor and normal tissues can be detected. We report the cloning and sequencing of two fragments detectable in two-dimensional separations of genomic DNA of neuroblastomas. These fragments were found to be a part of repetitive units that exhibited demethylation in neuroblastoma relative to other tumor types. Our finding of a distinct pattern of methylation of repetitive units in neuroblastoma suggests that altered methylation at certain loci may contribute to the biology of this tumor. Genes Chromosom Cancer 17:234–244 (1996). © 1996 Wiley-Liss, Inc. 相似文献
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