Frequent hypomethylation in Wilms tumors of pericentromeric DNA in chromosomes 1 and 16

Rearrangements in the pericentromeric heterochromatin of chromosome 1 or 16 are often found in many types of cancers, including Wilms tumors, and have been suggested to contribute to oncogenesis or tumor progression. The onco genic potential of these rearrangements has been ascribed to the resulting chromosome arm imbalances affecting the dosage of tumor suppressor genes or protooncogenes. Because DNA hypomethylation has been linked to rearrangeme nts in the pericentromeric regions of chromosome 1 and 16 in two types of n on-cancer cell populations, we examined methylation of normally highly meth ylated satellite DNA sequences in these regions in Wilms tumors. Hypomethyl ation was found to be frequent in juxtacentromeric (satellite 2) sequences and, especially, in centromeric (satellite alpha) sequences of chromosome 1 . Hypomethylation of satellite 2 DNA of chromosome 16 showed a high degree of concordance with that of satellite 2 DNA of chromosome 1. We discuss the relationship of this satellite DNA hypomethylation in Wilms tumors to chro mosome aberrations, as determined by assays for loss of heterozygosity. (C) Elsevier Science Inc., 1999. All rights reserved.