Cargando…
Mutations in normal tissues—some diagnostic and clinical implications
BACKGROUND: It has long been known that mutations are at the core of many diseases, most notably cancer. Mutational analysis of tissues and fluids is useful for cancer and other disease diagnosis and management. MAIN BODY: The prevailing cancer development hypothesis posits that cancer originates fr...
Autores principales: | , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594459/ https://www.ncbi.nlm.nih.gov/pubmed/33115454 http://dx.doi.org/10.1186/s12916-020-01763-y |
_version_ | 1783601642387537920 |
---|---|
author | Fiala, Clare Diamandis, Eleftherios P. |
author_facet | Fiala, Clare Diamandis, Eleftherios P. |
author_sort | Fiala, Clare |
collection | PubMed |
description | BACKGROUND: It has long been known that mutations are at the core of many diseases, most notably cancer. Mutational analysis of tissues and fluids is useful for cancer and other disease diagnosis and management. MAIN BODY: The prevailing cancer development hypothesis posits that cancer originates from mutations in cancer-driving genes that accumulate in tissues over time. These mutations then confer special characteristics to cancer cells, known as the hallmarks of cancer. Mutations in specific driver genes can lead to the formation of cancerous subclones and mutation risk increases with age. New research has revealed an unexpectedly large number of mutations in normal tissues; these findings could have significant implications to the understanding of the pathobiology of cancer and for disease diagnosis and therapy. Here, we discuss how the prevalence of mutations in normal tissues provides novel and relevant insights about clonal development in cancer and other diseases. Specifically, this review will focus on discussing mutations in normal tissues in the context of developing specific, circulating tumor DNA (ctDNA) tests for cancer, and evaluating clonal hematopoiesis as a predictor of blood cancers and cardiovascular pathology, as well as their implications to the phenomena of neural mosaicism in the context of Alzheimer’s disease. CONCLUSIONS: In view of these new findings, the fundamental differences between the accumulation of genetic alterations in healthy, aging tissues compared to cancer and cardiovascular or neural diseases will need to be better delineated in the future. |
format | Online Article Text |
id | pubmed-7594459 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-75944592020-10-30 Mutations in normal tissues—some diagnostic and clinical implications Fiala, Clare Diamandis, Eleftherios P. BMC Med Review BACKGROUND: It has long been known that mutations are at the core of many diseases, most notably cancer. Mutational analysis of tissues and fluids is useful for cancer and other disease diagnosis and management. MAIN BODY: The prevailing cancer development hypothesis posits that cancer originates from mutations in cancer-driving genes that accumulate in tissues over time. These mutations then confer special characteristics to cancer cells, known as the hallmarks of cancer. Mutations in specific driver genes can lead to the formation of cancerous subclones and mutation risk increases with age. New research has revealed an unexpectedly large number of mutations in normal tissues; these findings could have significant implications to the understanding of the pathobiology of cancer and for disease diagnosis and therapy. Here, we discuss how the prevalence of mutations in normal tissues provides novel and relevant insights about clonal development in cancer and other diseases. Specifically, this review will focus on discussing mutations in normal tissues in the context of developing specific, circulating tumor DNA (ctDNA) tests for cancer, and evaluating clonal hematopoiesis as a predictor of blood cancers and cardiovascular pathology, as well as their implications to the phenomena of neural mosaicism in the context of Alzheimer’s disease. CONCLUSIONS: In view of these new findings, the fundamental differences between the accumulation of genetic alterations in healthy, aging tissues compared to cancer and cardiovascular or neural diseases will need to be better delineated in the future. BioMed Central 2020-10-29 /pmc/articles/PMC7594459/ /pubmed/33115454 http://dx.doi.org/10.1186/s12916-020-01763-y Text en © The Author(s) 2020 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data. |
spellingShingle | Review Fiala, Clare Diamandis, Eleftherios P. Mutations in normal tissues—some diagnostic and clinical implications |
title | Mutations in normal tissues—some diagnostic and clinical implications |
title_full | Mutations in normal tissues—some diagnostic and clinical implications |
title_fullStr | Mutations in normal tissues—some diagnostic and clinical implications |
title_full_unstemmed | Mutations in normal tissues—some diagnostic and clinical implications |
title_short | Mutations in normal tissues—some diagnostic and clinical implications |
title_sort | mutations in normal tissues—some diagnostic and clinical implications |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594459/ https://www.ncbi.nlm.nih.gov/pubmed/33115454 http://dx.doi.org/10.1186/s12916-020-01763-y |
work_keys_str_mv | AT fialaclare mutationsinnormaltissuessomediagnosticandclinicalimplications AT diamandiseleftheriosp mutationsinnormaltissuessomediagnosticandclinicalimplications |