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Inferring modes of evolution from colorectal cancer with residual polyp of origin
Besides the classical evolutionary model of colorectal cancer (CRC) defined by the stepwise accumulation of mutations in which normal epithelium transforms through an intermediary polyp stage to cancer, a few studies have proposed alternative modes of evolution (MOE): early eruptive subclonal expans...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805514/ https://www.ncbi.nlm.nih.gov/pubmed/29467928 http://dx.doi.org/10.18632/oncotarget.23687 |
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author | Kim, Minsoo Druliner, Brooke R. Vasmatzis, Nikolaos Bae, Taejeong Chia, Nicholas Abyzov, Alexej Boardman, Lisa A. |
author_facet | Kim, Minsoo Druliner, Brooke R. Vasmatzis, Nikolaos Bae, Taejeong Chia, Nicholas Abyzov, Alexej Boardman, Lisa A. |
author_sort | Kim, Minsoo |
collection | PubMed |
description | Besides the classical evolutionary model of colorectal cancer (CRC) defined by the stepwise accumulation of mutations in which normal epithelium transforms through an intermediary polyp stage to cancer, a few studies have proposed alternative modes of evolution (MOE): early eruptive subclonal expansion, branching of the subclones in parallel evolution, and neutral evolution. However, frequencies of MOEs and their connection to mutational characteristics of cancer remain elusive. In this study, we analyzed patterns of somatic single nucleotide variations (SNVs) and copy number aberrations (CNAs) in CRC with residual polyp of origin from 13 patients in order to determine this relationship. For each MOE we defined an expected pattern with characteristic features of allele frequency distributions for SNVs in cancers and their matching adenomas. From these distinct patterns, we then assigned an MOE to each CRC case and found that stepwise progression was the most common (70% of cases). We found that CRC with the same MOE may exhibit different mutational spectra, suggesting that different mutational mechanisms can result in the same MOE. Inversely, cancers with different MOEs can have the same mutational spectrum, suggesting that the same mutational mechanism can lead to different MOEs. The types of somatic substitutions, distribution of CNAs across genome, and mutated pathways did not correlate with MOEs. As this could be due to small sample size, these relations warrant further investigation. Our study paves the way to connect MOE with clinical and mutational characteristics not only in CRC but also to neoplastic transformation in other cancers. |
format | Online Article Text |
id | pubmed-5805514 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-58055142018-02-21 Inferring modes of evolution from colorectal cancer with residual polyp of origin Kim, Minsoo Druliner, Brooke R. Vasmatzis, Nikolaos Bae, Taejeong Chia, Nicholas Abyzov, Alexej Boardman, Lisa A. Oncotarget Research Paper Besides the classical evolutionary model of colorectal cancer (CRC) defined by the stepwise accumulation of mutations in which normal epithelium transforms through an intermediary polyp stage to cancer, a few studies have proposed alternative modes of evolution (MOE): early eruptive subclonal expansion, branching of the subclones in parallel evolution, and neutral evolution. However, frequencies of MOEs and their connection to mutational characteristics of cancer remain elusive. In this study, we analyzed patterns of somatic single nucleotide variations (SNVs) and copy number aberrations (CNAs) in CRC with residual polyp of origin from 13 patients in order to determine this relationship. For each MOE we defined an expected pattern with characteristic features of allele frequency distributions for SNVs in cancers and their matching adenomas. From these distinct patterns, we then assigned an MOE to each CRC case and found that stepwise progression was the most common (70% of cases). We found that CRC with the same MOE may exhibit different mutational spectra, suggesting that different mutational mechanisms can result in the same MOE. Inversely, cancers with different MOEs can have the same mutational spectrum, suggesting that the same mutational mechanism can lead to different MOEs. The types of somatic substitutions, distribution of CNAs across genome, and mutated pathways did not correlate with MOEs. As this could be due to small sample size, these relations warrant further investigation. Our study paves the way to connect MOE with clinical and mutational characteristics not only in CRC but also to neoplastic transformation in other cancers. Impact Journals LLC 2017-12-26 /pmc/articles/PMC5805514/ /pubmed/29467928 http://dx.doi.org/10.18632/oncotarget.23687 Text en Copyright: © 2018 Kim et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Kim, Minsoo Druliner, Brooke R. Vasmatzis, Nikolaos Bae, Taejeong Chia, Nicholas Abyzov, Alexej Boardman, Lisa A. Inferring modes of evolution from colorectal cancer with residual polyp of origin |
title | Inferring modes of evolution from colorectal cancer with residual polyp of origin |
title_full | Inferring modes of evolution from colorectal cancer with residual polyp of origin |
title_fullStr | Inferring modes of evolution from colorectal cancer with residual polyp of origin |
title_full_unstemmed | Inferring modes of evolution from colorectal cancer with residual polyp of origin |
title_short | Inferring modes of evolution from colorectal cancer with residual polyp of origin |
title_sort | inferring modes of evolution from colorectal cancer with residual polyp of origin |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5805514/ https://www.ncbi.nlm.nih.gov/pubmed/29467928 http://dx.doi.org/10.18632/oncotarget.23687 |
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