Cargando…
The somatic mutation landscape of the human body
BACKGROUND: Somatic mutations in healthy tissues contribute to aging, neurodegeneration, and cancer initiation, yet they remain largely uncharacterized. RESULTS: To gain a better understanding of the genome-wide distribution and functional impact of somatic mutations, we leverage the genomic informa...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930685/ https://www.ncbi.nlm.nih.gov/pubmed/31874648 http://dx.doi.org/10.1186/s13059-019-1919-5 |
_version_ | 1783482950251184128 |
---|---|
author | García-Nieto, Pablo E. Morrison, Ashby J. Fraser, Hunter B. |
author_facet | García-Nieto, Pablo E. Morrison, Ashby J. Fraser, Hunter B. |
author_sort | García-Nieto, Pablo E. |
collection | PubMed |
description | BACKGROUND: Somatic mutations in healthy tissues contribute to aging, neurodegeneration, and cancer initiation, yet they remain largely uncharacterized. RESULTS: To gain a better understanding of the genome-wide distribution and functional impact of somatic mutations, we leverage the genomic information contained in the transcriptome to uniformly call somatic mutations from over 7500 tissue samples, representing 36 distinct tissues. This catalog, containing over 280,000 mutations, reveals a wide diversity of tissue-specific mutation profiles associated with gene expression levels and chromatin states. For example, lung samples with low expression of the mismatch-repair gene MLH1 show a mutation signature of deficient mismatch repair. In addition, we find pervasive negative selection acting on missense and nonsense mutations, except for mutations previously observed in cancer samples, which are under positive selection and are highly enriched in many healthy tissues. CONCLUSIONS: These findings reveal fundamental patterns of tissue-specific somatic evolution and shed light on aging and the earliest stages of tumorigenesis. |
format | Online Article Text |
id | pubmed-6930685 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-69306852019-12-30 The somatic mutation landscape of the human body García-Nieto, Pablo E. Morrison, Ashby J. Fraser, Hunter B. Genome Biol Research BACKGROUND: Somatic mutations in healthy tissues contribute to aging, neurodegeneration, and cancer initiation, yet they remain largely uncharacterized. RESULTS: To gain a better understanding of the genome-wide distribution and functional impact of somatic mutations, we leverage the genomic information contained in the transcriptome to uniformly call somatic mutations from over 7500 tissue samples, representing 36 distinct tissues. This catalog, containing over 280,000 mutations, reveals a wide diversity of tissue-specific mutation profiles associated with gene expression levels and chromatin states. For example, lung samples with low expression of the mismatch-repair gene MLH1 show a mutation signature of deficient mismatch repair. In addition, we find pervasive negative selection acting on missense and nonsense mutations, except for mutations previously observed in cancer samples, which are under positive selection and are highly enriched in many healthy tissues. CONCLUSIONS: These findings reveal fundamental patterns of tissue-specific somatic evolution and shed light on aging and the earliest stages of tumorigenesis. BioMed Central 2019-12-24 /pmc/articles/PMC6930685/ /pubmed/31874648 http://dx.doi.org/10.1186/s13059-019-1919-5 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research García-Nieto, Pablo E. Morrison, Ashby J. Fraser, Hunter B. The somatic mutation landscape of the human body |
title | The somatic mutation landscape of the human body |
title_full | The somatic mutation landscape of the human body |
title_fullStr | The somatic mutation landscape of the human body |
title_full_unstemmed | The somatic mutation landscape of the human body |
title_short | The somatic mutation landscape of the human body |
title_sort | somatic mutation landscape of the human body |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930685/ https://www.ncbi.nlm.nih.gov/pubmed/31874648 http://dx.doi.org/10.1186/s13059-019-1919-5 |
work_keys_str_mv | AT garcianietopabloe thesomaticmutationlandscapeofthehumanbody AT morrisonashbyj thesomaticmutationlandscapeofthehumanbody AT fraserhunterb thesomaticmutationlandscapeofthehumanbody AT garcianietopabloe somaticmutationlandscapeofthehumanbody AT morrisonashbyj somaticmutationlandscapeofthehumanbody AT fraserhunterb somaticmutationlandscapeofthehumanbody |