Satellite DNA hypomethylation in karyotyped Wilms tumors.
Previously, a high percentage of Wilms tumors was found to be hypomethylated in the unusually long region of pericentromeric satellite DNA on chromosome 1. We now show that these pediatric cancers are also frequently hypomethylated in centromeric satellite DNA throughout the genome and compare satellite DNA hypomethylation with chromosome rearrangements. Relative to normal somatic tissues, 83% of the tumors were hypomethylated in centromeric satellite alpha DNA. This was assessed by blot hybridization under low-stringency conditions after digestion with CpG methylation-sensitive restriction endonucleases. Similar results were obtained with different enzymes, indicating generalized hypomethylation of centromeric DNA. Hypomethylation of another heterochromatic sequence, juxtacentromeric satellite 2 DNA of chromosome 1, was observed in 51% of the tumors. By cytogenetic analysis, rearrangements in the centromeric or juxtacentromeric heterochromatin of chromosome 1 were the most frequent structural aberration and were seen in 14% of the tumors. Tumors with such rearrangements had hypomethylation of satellite DNA in the pericentromeric region. These results show a high degree of targeting of DNA hypomethylation to centromeric and juxtacentromeric satellite DNA sequences in cancer and are consistent with satellite DNA hypomethylation contributing to, but not sufficing for, karyotypic instability in cancer and possibly playing other roles in carcinogenesis.
Ehrlich
Melanie
M
Tulane Cancer Center and Human Genetics Program, Tulane Medical School, New Orleans, LA, USA. ehrlich@tulane.edu
Hopkins
Nancy Eddy
NE
Jiang
Guanchao
G
Dome
Jeffrey S
JS
Yu
Mimi C
MC
Woods
Christian B
CB
Tomlinson
Gail E
GE
Chintagumpala
Murali
M
Champagne
Martin
M
Dillerg
Lisa
L
Parham
David M
DM
Sawyer
Jeffrey
J
D002503:Centromere / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002878:Chromosomes, Human, Pair 1; D002879:Chromosomes, Human, Pair 10; D019175:DNA Methylation; D004276:DNA, Satellite / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007621:Karyotyping; D007680:Kidney Neoplasms / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics*
D004276:DNA, Satellite