DNA hypomethylation affects cancer-related biological functions and genes relevant in neuroblastoma pathogenesis.
Neuroblastoma (NB) pathogenesis has been reported to be closely associated with numerous genetic alterations. However, underlying DNA methylation patterns have not been extensively studied in this developmental malignancy. Here, we generated microarray-based DNA methylation profiles of primary neuro...
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oai:doaj.org-article:e2569acc34bf4ceebe718058e8732f712021-11-18T08:09:47ZDNA hypomethylation affects cancer-related biological functions and genes relevant in neuroblastoma pathogenesis.1932-620310.1371/journal.pone.0048401https://doaj.org/article/e2569acc34bf4ceebe718058e8732f712012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23144874/?tool=EBIhttps://doaj.org/toc/1932-6203Neuroblastoma (NB) pathogenesis has been reported to be closely associated with numerous genetic alterations. However, underlying DNA methylation patterns have not been extensively studied in this developmental malignancy. Here, we generated microarray-based DNA methylation profiles of primary neuroblastic tumors. Stringent supervised differential methylation analyses allowed us to identify epigenetic changes characteristic for NB tumors as well as for clinical and biological subtypes of NB. We observed that gene-specific loss of DNA methylation is more prevalent than promoter hypermethylation. Remarkably, such hypomethylation affected cancer-related biological functions and genes relevant to NB pathogenesis such as CCND1, SPRR3, BTC, EGF and FGF6. In particular, differential methylation in CCND1 affected mostly an evolutionary conserved functionally relevant 3' untranslated region, suggesting that hypomethylation outside promoter regions may play a role in NB pathogenesis. Hypermethylation targeted genes involved in cell development and proliferation such as RASSF1A, POU2F2 or HOXD3, among others. The results derived from this study provide new candidate epigenetic biomarkers associated with NB as well as insights into the molecular pathogenesis of this tumor, which involves a marked gene-specific hypomethylation.Gemma MayolJosé I Martín-SuberoJosé RíosAna QueirosMarta KulisMariona SuñolManel EstellerSoledad GómezIdoia GarciaCarmen de TorresEva RodríguezPatricia GalvánJaume MoraCinzia LavarinoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e48401 (2012) |
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Medicine R Science Q |
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Medicine R Science Q Gemma Mayol José I Martín-Subero José Ríos Ana Queiros Marta Kulis Mariona Suñol Manel Esteller Soledad Gómez Idoia Garcia Carmen de Torres Eva Rodríguez Patricia Galván Jaume Mora Cinzia Lavarino DNA hypomethylation affects cancer-related biological functions and genes relevant in neuroblastoma pathogenesis. |
| description |
Neuroblastoma (NB) pathogenesis has been reported to be closely associated with numerous genetic alterations. However, underlying DNA methylation patterns have not been extensively studied in this developmental malignancy. Here, we generated microarray-based DNA methylation profiles of primary neuroblastic tumors. Stringent supervised differential methylation analyses allowed us to identify epigenetic changes characteristic for NB tumors as well as for clinical and biological subtypes of NB. We observed that gene-specific loss of DNA methylation is more prevalent than promoter hypermethylation. Remarkably, such hypomethylation affected cancer-related biological functions and genes relevant to NB pathogenesis such as CCND1, SPRR3, BTC, EGF and FGF6. In particular, differential methylation in CCND1 affected mostly an evolutionary conserved functionally relevant 3' untranslated region, suggesting that hypomethylation outside promoter regions may play a role in NB pathogenesis. Hypermethylation targeted genes involved in cell development and proliferation such as RASSF1A, POU2F2 or HOXD3, among others. The results derived from this study provide new candidate epigenetic biomarkers associated with NB as well as insights into the molecular pathogenesis of this tumor, which involves a marked gene-specific hypomethylation. |
| format |
article |
| author |
Gemma Mayol José I Martín-Subero José Ríos Ana Queiros Marta Kulis Mariona Suñol Manel Esteller Soledad Gómez Idoia Garcia Carmen de Torres Eva Rodríguez Patricia Galván Jaume Mora Cinzia Lavarino |
| author_facet |
Gemma Mayol José I Martín-Subero José Ríos Ana Queiros Marta Kulis Mariona Suñol Manel Esteller Soledad Gómez Idoia Garcia Carmen de Torres Eva Rodríguez Patricia Galván Jaume Mora Cinzia Lavarino |
| author_sort |
Gemma Mayol |
| title |
DNA hypomethylation affects cancer-related biological functions and genes relevant in neuroblastoma pathogenesis. |
| title_short |
DNA hypomethylation affects cancer-related biological functions and genes relevant in neuroblastoma pathogenesis. |
| title_full |
DNA hypomethylation affects cancer-related biological functions and genes relevant in neuroblastoma pathogenesis. |
| title_fullStr |
DNA hypomethylation affects cancer-related biological functions and genes relevant in neuroblastoma pathogenesis. |
| title_full_unstemmed |
DNA hypomethylation affects cancer-related biological functions and genes relevant in neuroblastoma pathogenesis. |
| title_sort |
dna hypomethylation affects cancer-related biological functions and genes relevant in neuroblastoma pathogenesis. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/e2569acc34bf4ceebe718058e8732f71 |
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