DEMETHYLATION OF REPETITIVE DNA-SEQUENCES IN NEUROBLASTOMA

Altered genomic methylcytosine content has been described for a number of tumor types, including neuroblastoma However, it remains to be det ermined 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 analysi s of two-dimensional separations of human genomic restriction fragment s, Through the use of methylation-sensitive restriction enzymes, methy lation differences in genomic DNA between tumor and normal tissues can be detected, We report the cloning and sequencing of two fragments de tectable in two-dimensional separations of genomic DNA of neuroblastom as. These fragments were found to be a part of repetitive units that e xhibited 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. (C) 1996 Wiley-Liss, Inc.