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Pan-cancer analysis of somatic mutations in miRNA genes

BACKGROUND: miRNAs are considered important players in oncogenesis, serving either as oncomiRs or suppressormiRs. Although the accumulation of somatic alterations is an intrinsic aspect of cancer development and many important cancer-driving mutations have been identified in protein-coding genes, th...

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Autores principales: Urbanek-Trzeciak, Martyna O., Galka-Marciniak, Paulina, Nawrocka, Paulina M., Kowal, Ewelina, Szwec, Sylwia, Giefing, Maciej, Kozlowski, Piotr
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648123/
https://www.ncbi.nlm.nih.gov/pubmed/33038763
http://dx.doi.org/10.1016/j.ebiom.2020.103051
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author Urbanek-Trzeciak, Martyna O.
Galka-Marciniak, Paulina
Nawrocka, Paulina M.
Kowal, Ewelina
Szwec, Sylwia
Giefing, Maciej
Kozlowski, Piotr
author_facet Urbanek-Trzeciak, Martyna O.
Galka-Marciniak, Paulina
Nawrocka, Paulina M.
Kowal, Ewelina
Szwec, Sylwia
Giefing, Maciej
Kozlowski, Piotr
author_sort Urbanek-Trzeciak, Martyna O.
collection PubMed
description BACKGROUND: miRNAs are considered important players in oncogenesis, serving either as oncomiRs or suppressormiRs. Although the accumulation of somatic alterations is an intrinsic aspect of cancer development and many important cancer-driving mutations have been identified in protein-coding genes, the area of functional somatic mutations in miRNA genes is heavily understudied. METHODS: Here, based on the analysis of large genomic datasets, mostly the whole-exome sequencing of over 10,000 cancer/normal sample pairs deposited within the TCGA repository, we undertook an analysis of somatic mutations in miRNA genes. FINDINGS: We identified and characterized over 10,000 somatic mutations and showed that some of the miRNA genes are overmutated in Pan-Cancer and/or specific cancers. Nonrandom occurrence of the identified mutations was confirmed by a strong association of overmutated miRNA genes with KEGG pathways, most of which were related to specific cancer types or cancer-related processes. Additionally, we showed that mutations in some of the overmutated genes correlate with miRNA expression, cancer staging, and patient survival. INTERPRETATION: Our study is the first comprehensive Pan-Cancer study of cancer somatic mutations in miRNA genes. It may help to understand the consequences of mutations in miRNA genes and the identification of miRNA functional mutations. The results may also be the first step (form the basis and provide the resources) in the development of computational and/or statistical approaches/tools dedicated to the identification of cancer-driver miRNA genes. FUNDING: This work was supported by research grants from the Polish National Science Centre 2016/22/A/NZ2/00184 and 2015/17/N/NZ3/03629.
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spelling pubmed-76481232020-11-16 Pan-cancer analysis of somatic mutations in miRNA genes Urbanek-Trzeciak, Martyna O. Galka-Marciniak, Paulina Nawrocka, Paulina M. Kowal, Ewelina Szwec, Sylwia Giefing, Maciej Kozlowski, Piotr EBioMedicine Research Paper BACKGROUND: miRNAs are considered important players in oncogenesis, serving either as oncomiRs or suppressormiRs. Although the accumulation of somatic alterations is an intrinsic aspect of cancer development and many important cancer-driving mutations have been identified in protein-coding genes, the area of functional somatic mutations in miRNA genes is heavily understudied. METHODS: Here, based on the analysis of large genomic datasets, mostly the whole-exome sequencing of over 10,000 cancer/normal sample pairs deposited within the TCGA repository, we undertook an analysis of somatic mutations in miRNA genes. FINDINGS: We identified and characterized over 10,000 somatic mutations and showed that some of the miRNA genes are overmutated in Pan-Cancer and/or specific cancers. Nonrandom occurrence of the identified mutations was confirmed by a strong association of overmutated miRNA genes with KEGG pathways, most of which were related to specific cancer types or cancer-related processes. Additionally, we showed that mutations in some of the overmutated genes correlate with miRNA expression, cancer staging, and patient survival. INTERPRETATION: Our study is the first comprehensive Pan-Cancer study of cancer somatic mutations in miRNA genes. It may help to understand the consequences of mutations in miRNA genes and the identification of miRNA functional mutations. The results may also be the first step (form the basis and provide the resources) in the development of computational and/or statistical approaches/tools dedicated to the identification of cancer-driver miRNA genes. FUNDING: This work was supported by research grants from the Polish National Science Centre 2016/22/A/NZ2/00184 and 2015/17/N/NZ3/03629. Elsevier 2020-10-07 /pmc/articles/PMC7648123/ /pubmed/33038763 http://dx.doi.org/10.1016/j.ebiom.2020.103051 Text en © 2020 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Urbanek-Trzeciak, Martyna O.
Galka-Marciniak, Paulina
Nawrocka, Paulina M.
Kowal, Ewelina
Szwec, Sylwia
Giefing, Maciej
Kozlowski, Piotr
Pan-cancer analysis of somatic mutations in miRNA genes
title Pan-cancer analysis of somatic mutations in miRNA genes
title_full Pan-cancer analysis of somatic mutations in miRNA genes
title_fullStr Pan-cancer analysis of somatic mutations in miRNA genes
title_full_unstemmed Pan-cancer analysis of somatic mutations in miRNA genes
title_short Pan-cancer analysis of somatic mutations in miRNA genes
title_sort pan-cancer analysis of somatic mutations in mirna genes
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7648123/
https://www.ncbi.nlm.nih.gov/pubmed/33038763
http://dx.doi.org/10.1016/j.ebiom.2020.103051
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