Novel Mutation Hotspots within Non-Coding Regulatory Regions of the Chronic Lymphocytic Leukemia Genome

Mutations in non-coding DNA regions are increasingly recognized as cancer drivers. These mutations can modify gene expression in cis or by inducing high-order chormatin structure modifications with long-range effects. Previous analysis reported the detection of recurrent and functional non-coding DN...

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Autores principales: Mosquera Orgueira, Adrián, Rodríguez Antelo, Beatriz, Díaz Arias, José Ángel, Díaz Varela, Nicolás, Alonso Vence, Natalia, González Pérez, Marta Sonia, Bello López, José Luis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015923/
https://www.ncbi.nlm.nih.gov/pubmed/32051441
http://dx.doi.org/10.1038/s41598-020-59243-5
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author Mosquera Orgueira, Adrián
Rodríguez Antelo, Beatriz
Díaz Arias, José Ángel
Díaz Varela, Nicolás
Alonso Vence, Natalia
González Pérez, Marta Sonia
Bello López, José Luis
author_facet Mosquera Orgueira, Adrián
Rodríguez Antelo, Beatriz
Díaz Arias, José Ángel
Díaz Varela, Nicolás
Alonso Vence, Natalia
González Pérez, Marta Sonia
Bello López, José Luis
author_sort Mosquera Orgueira, Adrián
collection PubMed
description Mutations in non-coding DNA regions are increasingly recognized as cancer drivers. These mutations can modify gene expression in cis or by inducing high-order chormatin structure modifications with long-range effects. Previous analysis reported the detection of recurrent and functional non-coding DNA mutations in the chronic lymphocytic leukemia (CLL) genome, such as those in the 3′ untranslated region of NOTCH1 and in the PAX5 super-enhancer. In this report, we used whole genome sequencing data produced by the International Cancer Genome Consortium in order to analyze regions with previously reported regulatory activity. This approach enabled the identification of numerous recurrently mutated regions that were frequently positioned in the proximity of genes involved in immune and oncogenic pathways. By correlating these mutations with expression of their nearest genes, we detected significant transcriptional changes in genes such as PHF2 and S1PR2. More research is needed to clarify the function of these mutations in CLL, particularly those found in intergenic regions.
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spelling pubmed-70159232020-02-21 Novel Mutation Hotspots within Non-Coding Regulatory Regions of the Chronic Lymphocytic Leukemia Genome Mosquera Orgueira, Adrián Rodríguez Antelo, Beatriz Díaz Arias, José Ángel Díaz Varela, Nicolás Alonso Vence, Natalia González Pérez, Marta Sonia Bello López, José Luis Sci Rep Article Mutations in non-coding DNA regions are increasingly recognized as cancer drivers. These mutations can modify gene expression in cis or by inducing high-order chormatin structure modifications with long-range effects. Previous analysis reported the detection of recurrent and functional non-coding DNA mutations in the chronic lymphocytic leukemia (CLL) genome, such as those in the 3′ untranslated region of NOTCH1 and in the PAX5 super-enhancer. In this report, we used whole genome sequencing data produced by the International Cancer Genome Consortium in order to analyze regions with previously reported regulatory activity. This approach enabled the identification of numerous recurrently mutated regions that were frequently positioned in the proximity of genes involved in immune and oncogenic pathways. By correlating these mutations with expression of their nearest genes, we detected significant transcriptional changes in genes such as PHF2 and S1PR2. More research is needed to clarify the function of these mutations in CLL, particularly those found in intergenic regions. Nature Publishing Group UK 2020-02-12 /pmc/articles/PMC7015923/ /pubmed/32051441 http://dx.doi.org/10.1038/s41598-020-59243-5 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Mosquera Orgueira, Adrián
Rodríguez Antelo, Beatriz
Díaz Arias, José Ángel
Díaz Varela, Nicolás
Alonso Vence, Natalia
González Pérez, Marta Sonia
Bello López, José Luis
Novel Mutation Hotspots within Non-Coding Regulatory Regions of the Chronic Lymphocytic Leukemia Genome
title Novel Mutation Hotspots within Non-Coding Regulatory Regions of the Chronic Lymphocytic Leukemia Genome
title_full Novel Mutation Hotspots within Non-Coding Regulatory Regions of the Chronic Lymphocytic Leukemia Genome
title_fullStr Novel Mutation Hotspots within Non-Coding Regulatory Regions of the Chronic Lymphocytic Leukemia Genome
title_full_unstemmed Novel Mutation Hotspots within Non-Coding Regulatory Regions of the Chronic Lymphocytic Leukemia Genome
title_short Novel Mutation Hotspots within Non-Coding Regulatory Regions of the Chronic Lymphocytic Leukemia Genome
title_sort novel mutation hotspots within non-coding regulatory regions of the chronic lymphocytic leukemia genome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7015923/
https://www.ncbi.nlm.nih.gov/pubmed/32051441
http://dx.doi.org/10.1038/s41598-020-59243-5
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