Satellite DNA hypomethylation in karyotyped Wilms tumors

Melanie Ehrlich, Nancy Eddy Hopkins, Guanchao Jiang, Jeffrey S. Dome, Mimi C. Yu, Christian B. Woods, Gail E. Tomlinson, Murali Chintagumpala, Martin Champagne, Lisa Dillerg, David M. Parham, Jeffrey Sawyer

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

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 α 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.

Original languageEnglish (US)
Pages (from-to)97-105
Number of pages9
JournalCancer Genetics and Cytogenetics
Volume141
Issue number2
DOIs
StatePublished - Mar 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'Satellite DNA hypomethylation in karyotyped Wilms tumors'. Together they form a unique fingerprint.

Cite this