Hypermethylation of genomic 3.3-kb repeats is frequent event in HPV-positive cervical cancer
<p>Abstract</p> <p>Background</p> <p>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 i...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2009-05-01
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| Series: | BMC Medical Genomics |
| Online Access: | http://www.biomedcentral.com/1755-8794/2/30 |
| _version_ | 1818777122851782656 |
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| author | Kisseljova Natalia P Kisseljov Fjodor L Pavlova Larissa S Katargin Alexey N |
| author_facet | Kisseljova Natalia P Kisseljov Fjodor L Pavlova Larissa S Katargin Alexey N |
| author_sort | Kisseljova Natalia P |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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 genome-wide 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 <it>DUX </it>mRNA expression profile was also studied in these tissues.</p> <p>Methods</p> <p>The methylation status of 3.3-kb repeats was evaluated by Southern blot hybridization and bisulfite genomic sequencing. The expression of <it>DUX </it>mRNA was analyzed by RT-PCR and specificity of PCR products was confirmed by sequencing analysis.</p> <p>Results</p> <p>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 <it>DUX4 </it>and <it>DUX10 </it>genes in normal tissues and down-regulation of transcripts in 68% of tumors with and without 3.3-kb repeats hypermethylation.</p> <p>Conclusion</p> <p>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.</p> |
| first_indexed | 2024-12-18T11:23:49Z |
| format | Article |
| id | doaj.art-59ccac037a114c0bb07aca1e565273e1 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-12-18T11:23:49Z |
| publishDate | 2009-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-59ccac037a114c0bb07aca1e565273e12022-12-21T21:09:46ZengBMCBMC Medical Genomics1755-87942009-05-01213010.1186/1755-8794-2-30Hypermethylation of genomic 3.3-kb repeats is frequent event in HPV-positive cervical cancerKisseljova Natalia PKisseljov Fjodor LPavlova Larissa SKatargin Alexey N<p>Abstract</p> <p>Background</p> <p>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 genome-wide 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 <it>DUX </it>mRNA expression profile was also studied in these tissues.</p> <p>Methods</p> <p>The methylation status of 3.3-kb repeats was evaluated by Southern blot hybridization and bisulfite genomic sequencing. The expression of <it>DUX </it>mRNA was analyzed by RT-PCR and specificity of PCR products was confirmed by sequencing analysis.</p> <p>Results</p> <p>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 <it>DUX4 </it>and <it>DUX10 </it>genes in normal tissues and down-regulation of transcripts in 68% of tumors with and without 3.3-kb repeats hypermethylation.</p> <p>Conclusion</p> <p>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.</p>http://www.biomedcentral.com/1755-8794/2/30 |
| spellingShingle | Kisseljova Natalia P Kisseljov Fjodor L Pavlova Larissa S Katargin Alexey N Hypermethylation of genomic 3.3-kb repeats is frequent event in HPV-positive cervical cancer BMC Medical Genomics |
| title | Hypermethylation of genomic 3.3-kb repeats is frequent event in HPV-positive cervical cancer |
| title_full | Hypermethylation of genomic 3.3-kb repeats is frequent event in HPV-positive cervical cancer |
| title_fullStr | Hypermethylation of genomic 3.3-kb repeats is frequent event in HPV-positive cervical cancer |
| title_full_unstemmed | Hypermethylation of genomic 3.3-kb repeats is frequent event in HPV-positive cervical cancer |
| title_short | Hypermethylation of genomic 3.3-kb repeats is frequent event in HPV-positive cervical cancer |
| title_sort | hypermethylation of genomic 3 3 kb repeats is frequent event in hpv positive cervical cancer |
| url | http://www.biomedcentral.com/1755-8794/2/30 |
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