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The DNA methylation landscape of five pediatric-tumor types

Fewer DNA mutations have been identified in pediatric tumors than in adult tumors, suggesting that alternative tumorigenic mechanisms, including aberrant DNA methylation, may play a prominent role. In one epigenetic process of regulating gene expression, methyl groups are attached at the 5-carbon of...

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Autores principales: Parker, Alyssa C., Quinteros, Badí I., Piccolo, Stephen R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: PeerJ Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9190670/
https://www.ncbi.nlm.nih.gov/pubmed/35707123
http://dx.doi.org/10.7717/peerj.13516
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author Parker, Alyssa C.
Quinteros, Badí I.
Piccolo, Stephen R.
author_facet Parker, Alyssa C.
Quinteros, Badí I.
Piccolo, Stephen R.
author_sort Parker, Alyssa C.
collection PubMed
description Fewer DNA mutations have been identified in pediatric tumors than in adult tumors, suggesting that alternative tumorigenic mechanisms, including aberrant DNA methylation, may play a prominent role. In one epigenetic process of regulating gene expression, methyl groups are attached at the 5-carbon of the cytosine ring, leading to 5-methylcytosine (5mC). In somatic cells, 5mC occurs mostly in CpG islands, which are often within promoter regions. In Wilms tumors and acute myeloid leukemias, increased levels of epigenetic silencing have been associated with worse patient outcomes. However, to date, researchers have studied methylation primarily in adult tumors and for specific genes—but not on a pan-pediatric cancer scale. We addressed these gaps first by aggregating methylation data from 309 noncancerous samples, establishing baseline expectations for each probe and gene. Even though these samples represent diverse, noncancerous tissue types and population ancestral groups, methylation levels were consistent for most genes. Second, we compared tumor methylation levels against the baseline values for 489 pediatric tumors representing five cancer types: Wilms tumors, clear cell sarcomas of the kidney, rhabdoid tumors, neuroblastomas, and osteosarcomas. Tumor hypomethylation was more common than hypermethylation, and as many as 41.7% of genes were hypomethylated in a given tumor, compared to a maximum of 34.2% for hypermethylated genes. However, in known oncogenes, hypermethylation was more than twice as common as in other genes. We identified 139 probes (31 genes) that were differentially methylated between at least one tumor type and baseline levels, and 32 genes that were differentially methylated across the pediatric tumor types. We evaluated whether genomic events and aberrant methylation were mutually exclusive but did not find evidence of this phenomenon.
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spelling pubmed-91906702022-06-14 The DNA methylation landscape of five pediatric-tumor types Parker, Alyssa C. Quinteros, Badí I. Piccolo, Stephen R. PeerJ Bioinformatics Fewer DNA mutations have been identified in pediatric tumors than in adult tumors, suggesting that alternative tumorigenic mechanisms, including aberrant DNA methylation, may play a prominent role. In one epigenetic process of regulating gene expression, methyl groups are attached at the 5-carbon of the cytosine ring, leading to 5-methylcytosine (5mC). In somatic cells, 5mC occurs mostly in CpG islands, which are often within promoter regions. In Wilms tumors and acute myeloid leukemias, increased levels of epigenetic silencing have been associated with worse patient outcomes. However, to date, researchers have studied methylation primarily in adult tumors and for specific genes—but not on a pan-pediatric cancer scale. We addressed these gaps first by aggregating methylation data from 309 noncancerous samples, establishing baseline expectations for each probe and gene. Even though these samples represent diverse, noncancerous tissue types and population ancestral groups, methylation levels were consistent for most genes. Second, we compared tumor methylation levels against the baseline values for 489 pediatric tumors representing five cancer types: Wilms tumors, clear cell sarcomas of the kidney, rhabdoid tumors, neuroblastomas, and osteosarcomas. Tumor hypomethylation was more common than hypermethylation, and as many as 41.7% of genes were hypomethylated in a given tumor, compared to a maximum of 34.2% for hypermethylated genes. However, in known oncogenes, hypermethylation was more than twice as common as in other genes. We identified 139 probes (31 genes) that were differentially methylated between at least one tumor type and baseline levels, and 32 genes that were differentially methylated across the pediatric tumor types. We evaluated whether genomic events and aberrant methylation were mutually exclusive but did not find evidence of this phenomenon. PeerJ Inc. 2022-06-10 /pmc/articles/PMC9190670/ /pubmed/35707123 http://dx.doi.org/10.7717/peerj.13516 Text en © 2022 Parker et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.
spellingShingle Bioinformatics
Parker, Alyssa C.
Quinteros, Badí I.
Piccolo, Stephen R.
The DNA methylation landscape of five pediatric-tumor types
title The DNA methylation landscape of five pediatric-tumor types
title_full The DNA methylation landscape of five pediatric-tumor types
title_fullStr The DNA methylation landscape of five pediatric-tumor types
title_full_unstemmed The DNA methylation landscape of five pediatric-tumor types
title_short The DNA methylation landscape of five pediatric-tumor types
title_sort dna methylation landscape of five pediatric-tumor types
topic Bioinformatics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9190670/
https://www.ncbi.nlm.nih.gov/pubmed/35707123
http://dx.doi.org/10.7717/peerj.13516
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