Back to Search
Start Over
Hypermethylation of genomic 3.3-kb repeats is frequent event in HPV-positive cervical cancer.
- Source :
-
BMC Medical Genomics . 2009, Vol. 2, p1-11. 11p. 1 Diagram, 2 Charts, 3 Graphs. - Publication Year :
- 2009
-
Abstract
- Background: Large-scale screening methods are widely used to reveal cancer-specific DNA methylation markers. We previously identified non-satellite 3.3-kb repeats associated with facioscapulohumeral muscular dystrophy (FSHD) as hypermethylated in cervical cancer in genomewide screening. To determine whether hypermethylation of 3.3-kb repeats is a tumor-specific event and to evaluate frequency of this event in tumors, we investigated the 3.3-kb repeat methylation status in human papilloma virus (HPV)-positive cervical tumors, cancer cell lines, and normal cervical tissues. Open reading frames encoding DUX family proteins are contained within some 3.3-kb repeat units. The DUX mRNA expression profile was also studied in these tissues. Methods: The methylation status of 3.3-kb repeats was evaluated by Southern blot hybridization and bisulfite genomic sequencing. The expression of DUX mRNA was analyzed by RT-PCR and specificity of PCR products was confirmed by sequencing analysis. Results: Hypermethylation of 3.3-kb repeats relative to normal tissues was revealed for the first time in more than 50% (18/34) of cervical tumors and in 4 HPV-positive cervical cancer cell lines. Hypermethylation of 3.3-kb repeats was observed in tumors concurrently with or independently of hypomethylation of classical satellite 2 sequences (Sat2) that were hypomethylated in 75% (15/ 20) of cervical tumors. We have revealed the presence of transcripts highly homologous to DUX4 and DUX10 genes in normal tissues and down-regulation of transcripts in 68% of tumors with and without 3.3-kb repeats hypermethylation. Conclusion: Our results demonstrate that hypermethylation rather than hypomethylation of 3.3- kb repeats is the predominant event in HPV-associated cervical cancer and provide new insight into the epigenetic changes of repetitive DNA elements in carcinogenesis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17558794
- Volume :
- 2
- Database :
- Academic Search Index
- Journal :
- BMC Medical Genomics
- Publication Type :
- Academic Journal
- Accession number :
- 42309215
- Full Text :
- https://doi.org/10.1186/1755-8794-2-30