Cancer Risks Linked to the Bad Luck Hypothesis and Epigenomic Mutational Signatures
Exposure to pathogen infection, and occupational and environmental agents, contributes to induction of most types of cancer through different mechanisms. Cancer is defined and characterized by accumulation of mutations and epimutations that lead to changes in the cellular genome and epigenome. Accor...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-07-01
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| Series: | Epigenomes |
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| Online Access: | http://www.mdpi.com/2075-4655/2/3/13 |
| _version_ | 1797761768681897984 |
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| author | José E. Belizário |
| author_facet | José E. Belizário |
| author_sort | José E. Belizário |
| collection | DOAJ |
| description | Exposure to pathogen infection, and occupational and environmental agents, contributes to induction of most types of cancer through different mechanisms. Cancer is defined and characterized by accumulation of mutations and epimutations that lead to changes in the cellular genome and epigenome. According to a recent Bad Luck Hypothesis, random error mutations during DNA replication in a small population of stem cells may be implicated in two-thirds of variation of cancer risk in 25 organs and tissues. What determines stem cell vulnerability and risk of malignancy across the spectrum of organs, such as the brain, bone marrow, skeletal muscles, skin, and liver? Have stem cells pooled in particular tissues or organs evolved some critical ability to deal with DNA damage in the presence of extrinsic environmental factors? This paper describes how the complex replication and repair DNA systems control mutational events. In addition, recent advances on cancer epigenomic signatures and epigenetic mechanisms are discussed, which will guide future investigation of the origin of cancer initiating cells in tissue and organs in a clinical setting. |
| first_indexed | 2024-03-12T19:18:36Z |
| format | Article |
| id | doaj.art-4a49446877454166b057875004ec35a4 |
| institution | Directory Open Access Journal |
| issn | 2075-4655 |
| language | English |
| last_indexed | 2024-03-12T19:18:36Z |
| publishDate | 2018-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Epigenomes |
| spelling | doaj.art-4a49446877454166b057875004ec35a42023-08-02T05:22:00ZengMDPI AGEpigenomes2075-46552018-07-01231310.3390/epigenomes2030013epigenomes2030013Cancer Risks Linked to the Bad Luck Hypothesis and Epigenomic Mutational SignaturesJosé E. Belizário0Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo 05508-900, BrazilExposure to pathogen infection, and occupational and environmental agents, contributes to induction of most types of cancer through different mechanisms. Cancer is defined and characterized by accumulation of mutations and epimutations that lead to changes in the cellular genome and epigenome. According to a recent Bad Luck Hypothesis, random error mutations during DNA replication in a small population of stem cells may be implicated in two-thirds of variation of cancer risk in 25 organs and tissues. What determines stem cell vulnerability and risk of malignancy across the spectrum of organs, such as the brain, bone marrow, skeletal muscles, skin, and liver? Have stem cells pooled in particular tissues or organs evolved some critical ability to deal with DNA damage in the presence of extrinsic environmental factors? This paper describes how the complex replication and repair DNA systems control mutational events. In addition, recent advances on cancer epigenomic signatures and epigenetic mechanisms are discussed, which will guide future investigation of the origin of cancer initiating cells in tissue and organs in a clinical setting.http://www.mdpi.com/2075-4655/2/3/13cancercancer stem cellsDNA repairepigenomecancer risk |
| spellingShingle | José E. Belizário Cancer Risks Linked to the Bad Luck Hypothesis and Epigenomic Mutational Signatures Epigenomes cancer cancer stem cells DNA repair epigenome cancer risk |
| title | Cancer Risks Linked to the Bad Luck Hypothesis and Epigenomic Mutational Signatures |
| title_full | Cancer Risks Linked to the Bad Luck Hypothesis and Epigenomic Mutational Signatures |
| title_fullStr | Cancer Risks Linked to the Bad Luck Hypothesis and Epigenomic Mutational Signatures |
| title_full_unstemmed | Cancer Risks Linked to the Bad Luck Hypothesis and Epigenomic Mutational Signatures |
| title_short | Cancer Risks Linked to the Bad Luck Hypothesis and Epigenomic Mutational Signatures |
| title_sort | cancer risks linked to the bad luck hypothesis and epigenomic mutational signatures |
| topic | cancer cancer stem cells DNA repair epigenome cancer risk |
| url | http://www.mdpi.com/2075-4655/2/3/13 |
| work_keys_str_mv | AT joseebelizario cancerriskslinkedtothebadluckhypothesisandepigenomicmutationalsignatures |