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Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors
SIMPLE SUMMARY: About 7% of all children’s malignancies are represented by the embryonal renal cancer Wilms tumor (WT). Since methylation imprinting alterations at multiple loci dictated by chromosome copy-number variations have been recently demonstrated in adult cancers, we investigated the presen...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698742/ https://www.ncbi.nlm.nih.gov/pubmed/33217932 http://dx.doi.org/10.3390/cancers12113411 |
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author | Pignata, Laura Palumbo, Orazio Cerrato, Flavia Acurzio, Basilia de Álava, Enrique Roma, Josep Gallego, Soledad Mora, Jaume Carella, Massimo Riccio, Andrea Verde, Gaetano |
author_facet | Pignata, Laura Palumbo, Orazio Cerrato, Flavia Acurzio, Basilia de Álava, Enrique Roma, Josep Gallego, Soledad Mora, Jaume Carella, Massimo Riccio, Andrea Verde, Gaetano |
author_sort | Pignata, Laura |
collection | PubMed |
description | SIMPLE SUMMARY: About 7% of all children’s malignancies are represented by the embryonal renal cancer Wilms tumor (WT). Since methylation imprinting alterations at multiple loci dictated by chromosome copy-number variations have been recently demonstrated in adult cancers, we investigated the presence of similar alterations in pediatric malignancies. Our results demonstrated that 35% of WT cases were affected by methylation abnormalities of multiple imprinted loci. However, differently from adult cancers, they were associated with either chromosome aberrations or normal chromosome profiles. Epigenotype–phenotype correlations indicated that these epimutations were more frequent in highly aggressive tumors, suggesting the use of multiple methylation imprinting defects as a new informative marker for WT. ABSTRACT: The embryonal renal cancer Wilms tumor (WT) accounts for 7% of all children’s malignancies. Its most frequent molecular defect is represented by DNA methylation abnormalities at the imprinted 11p15.5 region. Multiple imprinted methylation alterations dictated by chromosome copy-number variations have been recently demonstrated in adult cancers, raising the question of whether multiple imprinted loci were also affected in WT. To address this issue, we analyzed DNA methylation and chromosome profiles of 7 imprinted loci in 48 WT samples. The results demonstrated that methylation abnormalities of multiple imprinted loci occurred in 35% of the cases, but that they were associated with either chromosome aberrations or normal chromosome profiles. Multiple imprinted methylation changes were correlated with tumor stage and presence of metastasis, indicating that these epimutations were more frequent in highly aggressive tumors. When chromosome profiles were affected, these alterations were extended to flanking cancer driver genes. Overall, this study demonstrates the presence of multiple imprinted methylation defects in aggressive WTs and suggests that the mechanism by which they arise in embryonal and adult cancers is different. |
format | Online Article Text |
id | pubmed-7698742 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76987422020-11-29 Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors Pignata, Laura Palumbo, Orazio Cerrato, Flavia Acurzio, Basilia de Álava, Enrique Roma, Josep Gallego, Soledad Mora, Jaume Carella, Massimo Riccio, Andrea Verde, Gaetano Cancers (Basel) Article SIMPLE SUMMARY: About 7% of all children’s malignancies are represented by the embryonal renal cancer Wilms tumor (WT). Since methylation imprinting alterations at multiple loci dictated by chromosome copy-number variations have been recently demonstrated in adult cancers, we investigated the presence of similar alterations in pediatric malignancies. Our results demonstrated that 35% of WT cases were affected by methylation abnormalities of multiple imprinted loci. However, differently from adult cancers, they were associated with either chromosome aberrations or normal chromosome profiles. Epigenotype–phenotype correlations indicated that these epimutations were more frequent in highly aggressive tumors, suggesting the use of multiple methylation imprinting defects as a new informative marker for WT. ABSTRACT: The embryonal renal cancer Wilms tumor (WT) accounts for 7% of all children’s malignancies. Its most frequent molecular defect is represented by DNA methylation abnormalities at the imprinted 11p15.5 region. Multiple imprinted methylation alterations dictated by chromosome copy-number variations have been recently demonstrated in adult cancers, raising the question of whether multiple imprinted loci were also affected in WT. To address this issue, we analyzed DNA methylation and chromosome profiles of 7 imprinted loci in 48 WT samples. The results demonstrated that methylation abnormalities of multiple imprinted loci occurred in 35% of the cases, but that they were associated with either chromosome aberrations or normal chromosome profiles. Multiple imprinted methylation changes were correlated with tumor stage and presence of metastasis, indicating that these epimutations were more frequent in highly aggressive tumors. When chromosome profiles were affected, these alterations were extended to flanking cancer driver genes. Overall, this study demonstrates the presence of multiple imprinted methylation defects in aggressive WTs and suggests that the mechanism by which they arise in embryonal and adult cancers is different. MDPI 2020-11-18 /pmc/articles/PMC7698742/ /pubmed/33217932 http://dx.doi.org/10.3390/cancers12113411 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Pignata, Laura Palumbo, Orazio Cerrato, Flavia Acurzio, Basilia de Álava, Enrique Roma, Josep Gallego, Soledad Mora, Jaume Carella, Massimo Riccio, Andrea Verde, Gaetano Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors |
title | Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors |
title_full | Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors |
title_fullStr | Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors |
title_full_unstemmed | Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors |
title_short | Both Epimutations and Chromosome Aberrations Affect Multiple Imprinted Loci in Aggressive Wilms Tumors |
title_sort | both epimutations and chromosome aberrations affect multiple imprinted loci in aggressive wilms tumors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698742/ https://www.ncbi.nlm.nih.gov/pubmed/33217932 http://dx.doi.org/10.3390/cancers12113411 |
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