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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Main Authors: 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
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23144874/?tool=EBI
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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
collection DOAJ
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.
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spelling doaj.art-e2569acc34bf4ceebe718058e8732f712022-12-21T21:43:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e4840110.1371/journal.pone.0048401DNA hypomethylation affects cancer-related biological functions and genes relevant in neuroblastoma pathogenesis.Gemma MayolJosé I Martín-SuberoJosé RíosAna QueirosMarta KulisMariona SuñolManel EstellerSoledad GómezIdoia GarciaCarmen de TorresEva RodríguezPatricia GalvánJaume MoraCinzia LavarinoNeuroblastoma (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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23144874/?tool=EBI
spellingShingle 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.
PLoS ONE
title 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_short 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
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23144874/?tool=EBI
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