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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Bibliographic Details
Published in:Scientific reports 2020-02, Vol.10 (1), p.2407-2407, Article 2407
Main Authors: Mosquera Orgueira, Adrián, Rodríguez Antelo, Beatriz, Díaz Arias, José Ángel, Díaz Varela, Nicolás, Alonso Vence, Natalia, González Pérez, Marta Sonia, Bello López, José Luis
Format: Article
Language:English
Subjects:
3' Untranslated Regions
Chronic lymphocytic leukemia
Deoxyribonucleic acid
DNA
DNA Mutational Analysis
DNA, Intergenic - genetics
Gene expression
Genomes
Homeodomain Proteins - genetics
Humans
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell - genetics
Lymphatic leukemia
Mutation
Mutation hot spots
Pax5 protein
PAX5 Transcription Factor - genetics
Receptor, Notch1 - genetics
Regulatory sequences
Regulatory Sequences, Nucleic Acid
Sphingosine-1-Phosphate Receptors - genetics
Transcription
Whole Genome Sequencing
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-59243-5