Analysis of mutations in tumor and normal adjacent tissue via fluorescence detection
© 2020 Wiley Periodicals LLC. Inflammation is a major risk factor for many types of cancer, including colorectal. There are two fundamentally different mechanisms by which inflammation can contribute to carcinogenesis. First, reactive oxygen and nitrogen species (RONS) can damage DNA to cause mutati...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022
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| Online Access: | https://hdl.handle.net/1721.1/139825.2 |
| _version_ | 1811072079739486208 |
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| author | Kay, Jennifer E Mirabal, Sheyla Briley, William E Kimoto, Takafumi Poutahidis, Theofilos Ragan, Timothy So, Peter T Wadduwage, Dushan N Erdman, Susan E Engelward, Bevin P |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Kay, Jennifer E Mirabal, Sheyla Briley, William E Kimoto, Takafumi Poutahidis, Theofilos Ragan, Timothy So, Peter T Wadduwage, Dushan N Erdman, Susan E Engelward, Bevin P |
| author_sort | Kay, Jennifer E |
| collection | MIT |
| description | © 2020 Wiley Periodicals LLC. Inflammation is a major risk factor for many types of cancer, including colorectal. There are two fundamentally different mechanisms by which inflammation can contribute to carcinogenesis. First, reactive oxygen and nitrogen species (RONS) can damage DNA to cause mutations that initiate cancer. Second, inflammatory cytokines and chemokines promote proliferation, migration, and invasion. Although it is known that inflammation-associated RONS can be mutagenic, the extent to which they induce mutations in intestinal stem cells has been little explored. Furthermore, it is now widely accepted that cancer is caused by successive rounds of clonal expansion with associated de novo mutations that further promote tumor development. As such, we aimed to understand the extent to which inflammation promotes clonal expansion in normal and tumor tissue. Using an engineered mouse model that is prone to cancer and within which mutant cells fluoresce, here we have explored the impact of inflammation on de novo mutagenesis and clonal expansion in normal and tumor tissue. While inflammation is strongly associated with susceptibility to cancer and a concomitant increase in the overall proportion of mutant cells in the tissue, we did not observe an increase in mutations in normal adjacent tissue. These results are consistent with opportunities for de novo mutations and clonal expansion during tumor growth, and they suggest protective mechanisms that suppress the risk of inflammation-induced accumulation of mutant cells in normal tissue. |
| first_indexed | 2024-09-23T09:00:35Z |
| format | Article |
| id | mit-1721.1/139825.2 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:00:35Z |
| publishDate | 2022 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/139825.22024-03-22T20:33:11Z Analysis of mutations in tumor and normal adjacent tissue via fluorescence detection Kay, Jennifer E Mirabal, Sheyla Briley, William E Kimoto, Takafumi Poutahidis, Theofilos Ragan, Timothy So, Peter T Wadduwage, Dushan N Erdman, Susan E Engelward, Bevin P Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Division of Comparative Medicine Massachusetts Institute of Technology. Department of Mechanical Engineering © 2020 Wiley Periodicals LLC. Inflammation is a major risk factor for many types of cancer, including colorectal. There are two fundamentally different mechanisms by which inflammation can contribute to carcinogenesis. First, reactive oxygen and nitrogen species (RONS) can damage DNA to cause mutations that initiate cancer. Second, inflammatory cytokines and chemokines promote proliferation, migration, and invasion. Although it is known that inflammation-associated RONS can be mutagenic, the extent to which they induce mutations in intestinal stem cells has been little explored. Furthermore, it is now widely accepted that cancer is caused by successive rounds of clonal expansion with associated de novo mutations that further promote tumor development. As such, we aimed to understand the extent to which inflammation promotes clonal expansion in normal and tumor tissue. Using an engineered mouse model that is prone to cancer and within which mutant cells fluoresce, here we have explored the impact of inflammation on de novo mutagenesis and clonal expansion in normal and tumor tissue. While inflammation is strongly associated with susceptibility to cancer and a concomitant increase in the overall proportion of mutant cells in the tissue, we did not observe an increase in mutations in normal adjacent tissue. These results are consistent with opportunities for de novo mutations and clonal expansion during tumor growth, and they suggest protective mechanisms that suppress the risk of inflammation-induced accumulation of mutant cells in normal tissue. 2022-02-01T18:57:06Z 2022-02-01T15:40:32Z 2022-02-01T18:57:06Z 2020-12 2020-12 2022-02-01T15:25:19Z Article http://purl.org/eprint/type/JournalArticle 1098-2280 0893-6692 https://hdl.handle.net/1721.1/139825.2 Kay, Jennifer E, Mirabal, Sheyla, Briley, William E, Kimoto, Takafumi, Poutahidis, Theofilos et al. 2021. "Analysis of mutations in tumor and normal adjacent tissue via fluorescence detection." Environmental and Molecular Mutagenesis, 62 (2). en http://dx.doi.org/10.1002/EM.22419 Environmental and Molecular Mutagenesis Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/octet-stream Wiley PMC |
| spellingShingle | Kay, Jennifer E Mirabal, Sheyla Briley, William E Kimoto, Takafumi Poutahidis, Theofilos Ragan, Timothy So, Peter T Wadduwage, Dushan N Erdman, Susan E Engelward, Bevin P Analysis of mutations in tumor and normal adjacent tissue via fluorescence detection |
| title | Analysis of mutations in tumor and normal adjacent tissue via fluorescence detection |
| title_full | Analysis of mutations in tumor and normal adjacent tissue via fluorescence detection |
| title_fullStr | Analysis of mutations in tumor and normal adjacent tissue via fluorescence detection |
| title_full_unstemmed | Analysis of mutations in tumor and normal adjacent tissue via fluorescence detection |
| title_short | Analysis of mutations in tumor and normal adjacent tissue via fluorescence detection |
| title_sort | analysis of mutations in tumor and normal adjacent tissue via fluorescence detection |
| url | https://hdl.handle.net/1721.1/139825.2 |
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