Frequent Hypomethylation in Wilms Tumors of Pericentromeric DNA in Chromosomes 1 and 16

DNA methylation in cancer: too much, but also too little

“…Hypomethylation of Chr1 Sat2 and of Chr16 Sat2 was usually concordant, which is consistent with their sequence homology. However, undermethylation of Chr1 Sat2 was also paralleled by hypomethylation of the above-described heterologous rDNA spacer in the acrocentric chromosomes' p-arms in the ten Wilms tumors analysed for methylation of both repeats (Qu et al, 1999b). In human hepatocellular carcinomas, the frequent hypomethylation of Sat2 DNA (Saito et al, 2001;Wong et al, 2001) was highly concordant with that of Sat3, the main DNA component of the long juxtacentromeric heterochromatin of Chr9 (Saito et al, 2001).…”

“…In human hepatocellular carcinomas, the frequent hypomethylation of Sat2 DNA (Saito et al, 2001;Wong et al, 2001) was highly concordant with that of Sat3, the main DNA component of the long juxtacentromeric heterochromatin of Chr9 (Saito et al, 2001). Sat2, Sat3, and Sata DNA sequences are normally hypomethylated in human sperm compared with a wide variety of normal postnatal somatic tissues just as the rDNA spacer sequence is (Qu et al, 1999b;Zhang et al, 1987). Moreover, in mice it has been shown that both oocyte and sperm DNAs are hypomethylated in satellite sequences (Chapman et al, 1984).…”

“…It is part of the nontranscribed intergenic spacer for the 45S ribosomal RNA gene repeat. In 5 out of 10 analysed Wilms tumors, it was hypomethylated compared with a variety of normal postnatal somatic tissues (Qu et al, 1999b). A different portion of this rDNA nontranscribed spacer was found to be undermethylated in one of two examined human lung cancers relative to adjacent 'normal' tissue in another study (Shiraishi et al, 1999).…”

DNA hypomethylation is prevalent even in low-grade breast cancers

“…8,9 By Southern blot analysis with a CpG methylation-sensitive restriction endonuclease, we have shown that satellite 2 DNA (Sat2), the main sequence in the long juxtacentromeric (centromere-adjacent) heterochromatin of chromosome 1 (Chr1), is often hypomethylated in breast adenocarcinomas and Wilms tumors as well as in ovarian epithelial carcinomas. [10][11][12] Hypomethylation of this satellite DNA at 1qh was strongly linked to hypomethylation of the highly homologous satellite DNA at 16qh (Chrl6 Sat2) in these three disparate types of cancer. Also, in human hepatocellular carcinomas, hypomethylation of Sat2 was highly concordant with that of Sat3, the main DNA component of the long juxtacentromeric heterochromatin of Chr9.…”

“…14 Interestingly, Sat2, Sat3, and Satα are hypomethylated in sperm DNA, and Sat2 and Sat3 are also invariably hypomethylated in cells from patients with the ICF syndrome (immunodeficiency, centromeric region instability, and facial anomalies; a DNA methyltransferase 3B deficiency disease). 10,11,[15][16][17] Studies of ICF lymphoid cells and normal cells treated with DNA methylation inhibitors suggest that DNA hypomethylation can favor pericentromeric rearrangements, including the formation of unstable multiradial chromosomes that may give rise to stable, unbalanced cancer-like DNA rearrangements. 15,16,18,19 This is consistent with a comparative genomic hybridization study showing a significant association between 1qh gain and Chr1 Sat2 hypomethylation in hepatocellular carcinomas.…”