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Clonal origins and parallel evolution of regionally synchronous colorectal adenoma and carcinoma
Although the colorectal adenoma-to-carcinoma sequence represents a classical cancer progression model, the evolution of the mutational landscape underlying this model is not fully understood. In this study, we analyzed eight synchronous pairs of colorectal high-grade adenomas and carcinomas, four mi...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695021/ https://www.ncbi.nlm.nih.gov/pubmed/26336987 |
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author | Kim, Tae-Min An, Chang Hyeok Rhee, Je-Keun Jung, Seung-Hyun Lee, Sung Hak Baek, In-Pyo Kim, Min Sung Lee, Sug Hyung Chung, Yeun-Jun |
author_facet | Kim, Tae-Min An, Chang Hyeok Rhee, Je-Keun Jung, Seung-Hyun Lee, Sung Hak Baek, In-Pyo Kim, Min Sung Lee, Sug Hyung Chung, Yeun-Jun |
author_sort | Kim, Tae-Min |
collection | PubMed |
description | Although the colorectal adenoma-to-carcinoma sequence represents a classical cancer progression model, the evolution of the mutational landscape underlying this model is not fully understood. In this study, we analyzed eight synchronous pairs of colorectal high-grade adenomas and carcinomas, four microsatellite-unstable (MSU) and four -stable (MSS) pairs, using whole-exome sequencing. In the MSU adenoma-carcinoma pairs, we observed no subclonal mutations in adenomas that became fixed in paired carcinomas, suggesting a ‘parallel’ evolution of synchronous adenoma-to-carcinoma, rather than a ‘stepwise’ evolution. The abundance of indel (in MSU and MSS pairs) and microsatellite instability (in MSU pairs) was noted in the later adenoma- or carcinoma-specific mutations, indicating that the mutational processes and functional constraints operative in early and late colorectal carcinogenesis are different. All MSU cases exhibited clonal, truncating mutations in ACVR2A, TGFBR2, and DNA mismatch repair genes, but none were present in APC or KRAS. In three MSS pairs, both APC and KRAS mutations were identified as both early and clonal events, often accompanying clonal copy number changes. An MSS case uniquely exhibited clonal ERBB2 amplification, followed by APC and TP53 mutations as carcinoma-specific events. Along with the previously unrecognized clonal origins of synchronous colorectal adenoma-carcinoma pairs, our study revealed that the preferred sequence of mutational events during colorectal carcinogenesis can be context-dependent. |
format | Online Article Text |
id | pubmed-4695021 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-46950212016-01-20 Clonal origins and parallel evolution of regionally synchronous colorectal adenoma and carcinoma Kim, Tae-Min An, Chang Hyeok Rhee, Je-Keun Jung, Seung-Hyun Lee, Sung Hak Baek, In-Pyo Kim, Min Sung Lee, Sug Hyung Chung, Yeun-Jun Oncotarget Research Paper Although the colorectal adenoma-to-carcinoma sequence represents a classical cancer progression model, the evolution of the mutational landscape underlying this model is not fully understood. In this study, we analyzed eight synchronous pairs of colorectal high-grade adenomas and carcinomas, four microsatellite-unstable (MSU) and four -stable (MSS) pairs, using whole-exome sequencing. In the MSU adenoma-carcinoma pairs, we observed no subclonal mutations in adenomas that became fixed in paired carcinomas, suggesting a ‘parallel’ evolution of synchronous adenoma-to-carcinoma, rather than a ‘stepwise’ evolution. The abundance of indel (in MSU and MSS pairs) and microsatellite instability (in MSU pairs) was noted in the later adenoma- or carcinoma-specific mutations, indicating that the mutational processes and functional constraints operative in early and late colorectal carcinogenesis are different. All MSU cases exhibited clonal, truncating mutations in ACVR2A, TGFBR2, and DNA mismatch repair genes, but none were present in APC or KRAS. In three MSS pairs, both APC and KRAS mutations were identified as both early and clonal events, often accompanying clonal copy number changes. An MSS case uniquely exhibited clonal ERBB2 amplification, followed by APC and TP53 mutations as carcinoma-specific events. Along with the previously unrecognized clonal origins of synchronous colorectal adenoma-carcinoma pairs, our study revealed that the preferred sequence of mutational events during colorectal carcinogenesis can be context-dependent. Impact Journals LLC 2015-08-07 /pmc/articles/PMC4695021/ /pubmed/26336987 Text en Copyright: © 2015 Kim et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Kim, Tae-Min An, Chang Hyeok Rhee, Je-Keun Jung, Seung-Hyun Lee, Sung Hak Baek, In-Pyo Kim, Min Sung Lee, Sug Hyung Chung, Yeun-Jun Clonal origins and parallel evolution of regionally synchronous colorectal adenoma and carcinoma |
title | Clonal origins and parallel evolution of regionally synchronous colorectal adenoma and carcinoma |
title_full | Clonal origins and parallel evolution of regionally synchronous colorectal adenoma and carcinoma |
title_fullStr | Clonal origins and parallel evolution of regionally synchronous colorectal adenoma and carcinoma |
title_full_unstemmed | Clonal origins and parallel evolution of regionally synchronous colorectal adenoma and carcinoma |
title_short | Clonal origins and parallel evolution of regionally synchronous colorectal adenoma and carcinoma |
title_sort | clonal origins and parallel evolution of regionally synchronous colorectal adenoma and carcinoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695021/ https://www.ncbi.nlm.nih.gov/pubmed/26336987 |
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