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Molecular characterization of colorectal adenomas with and without malignancy reveals distinguishing genome, transcriptome and methylome alterations
The majority of colorectal cancer (CRC) arises from precursor lesions known as polyps. The molecular determinants that distinguish benign from malignant polyps remain unclear. To molecularly characterize polyps, we utilized Cancer Adjacent Polyp (CAP) and Cancer Free Polyp (CFP) patients. CAPs had t...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816667/ https://www.ncbi.nlm.nih.gov/pubmed/29453410 http://dx.doi.org/10.1038/s41598-018-21525-4 |
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author | Druliner, Brooke R. Wang, Panwen Bae, Taejeong Baheti, Saurabh Slettedahl, Seth Mahoney, Douglas Vasmatzis, Nikolaos Xu, Hang Kim, Minsoo Bockol, Matthew O’Brien, Daniel Grill, Diane Warner, Nathaniel Munoz-Gomez, Miguel Kossick, Kimberlee Johnson, Ruth Mouchli, Mohamad Felmlee-Devine, Donna Washechek-Aletto, Jill Smyrk, Thomas Oberg, Ann Wang, Junwen Chia, Nicholas Abyzov, Alexej Ahlquist, David Boardman, Lisa A. |
author_facet | Druliner, Brooke R. Wang, Panwen Bae, Taejeong Baheti, Saurabh Slettedahl, Seth Mahoney, Douglas Vasmatzis, Nikolaos Xu, Hang Kim, Minsoo Bockol, Matthew O’Brien, Daniel Grill, Diane Warner, Nathaniel Munoz-Gomez, Miguel Kossick, Kimberlee Johnson, Ruth Mouchli, Mohamad Felmlee-Devine, Donna Washechek-Aletto, Jill Smyrk, Thomas Oberg, Ann Wang, Junwen Chia, Nicholas Abyzov, Alexej Ahlquist, David Boardman, Lisa A. |
author_sort | Druliner, Brooke R. |
collection | PubMed |
description | The majority of colorectal cancer (CRC) arises from precursor lesions known as polyps. The molecular determinants that distinguish benign from malignant polyps remain unclear. To molecularly characterize polyps, we utilized Cancer Adjacent Polyp (CAP) and Cancer Free Polyp (CFP) patients. CAPs had tissues from the residual polyp of origin and contiguous cancer; CFPs had polyp tissues matched to CAPs based on polyp size, histology and dysplasia. To determine whether molecular features distinguish CAPs and CFPs, we conducted Whole Genome Sequencing, RNA-seq, and RRBS on over 90 tissues from 31 patients. CAPs had significantly more mutations, altered expression and hypermethylation compared to CFPs. APC was significantly mutated in both polyp groups, but mutations in TP53, FBXW7, PIK3CA, KIAA1804 and SMAD2 were exclusive to CAPs. We found significant expression changes between CAPs and CFPs in GREM1, IGF2, CTGF, and PLAU, and both expression and methylation alterations in FES and HES1. Integrative analyses revealed 124 genes with alterations in at least two platforms, and ERBB3 and E2F8 showed aberrations specific to CAPs across all platforms. These findings provide a resource of molecular distinctions between polyps with and without cancer, which have the potential to enhance the diagnosis, risk assessment and management of polyps. |
format | Online Article Text |
id | pubmed-5816667 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58166672018-02-21 Molecular characterization of colorectal adenomas with and without malignancy reveals distinguishing genome, transcriptome and methylome alterations Druliner, Brooke R. Wang, Panwen Bae, Taejeong Baheti, Saurabh Slettedahl, Seth Mahoney, Douglas Vasmatzis, Nikolaos Xu, Hang Kim, Minsoo Bockol, Matthew O’Brien, Daniel Grill, Diane Warner, Nathaniel Munoz-Gomez, Miguel Kossick, Kimberlee Johnson, Ruth Mouchli, Mohamad Felmlee-Devine, Donna Washechek-Aletto, Jill Smyrk, Thomas Oberg, Ann Wang, Junwen Chia, Nicholas Abyzov, Alexej Ahlquist, David Boardman, Lisa A. Sci Rep Article The majority of colorectal cancer (CRC) arises from precursor lesions known as polyps. The molecular determinants that distinguish benign from malignant polyps remain unclear. To molecularly characterize polyps, we utilized Cancer Adjacent Polyp (CAP) and Cancer Free Polyp (CFP) patients. CAPs had tissues from the residual polyp of origin and contiguous cancer; CFPs had polyp tissues matched to CAPs based on polyp size, histology and dysplasia. To determine whether molecular features distinguish CAPs and CFPs, we conducted Whole Genome Sequencing, RNA-seq, and RRBS on over 90 tissues from 31 patients. CAPs had significantly more mutations, altered expression and hypermethylation compared to CFPs. APC was significantly mutated in both polyp groups, but mutations in TP53, FBXW7, PIK3CA, KIAA1804 and SMAD2 were exclusive to CAPs. We found significant expression changes between CAPs and CFPs in GREM1, IGF2, CTGF, and PLAU, and both expression and methylation alterations in FES and HES1. Integrative analyses revealed 124 genes with alterations in at least two platforms, and ERBB3 and E2F8 showed aberrations specific to CAPs across all platforms. These findings provide a resource of molecular distinctions between polyps with and without cancer, which have the potential to enhance the diagnosis, risk assessment and management of polyps. Nature Publishing Group UK 2018-02-16 /pmc/articles/PMC5816667/ /pubmed/29453410 http://dx.doi.org/10.1038/s41598-018-21525-4 Text en © The Author(s) 2018 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Druliner, Brooke R. Wang, Panwen Bae, Taejeong Baheti, Saurabh Slettedahl, Seth Mahoney, Douglas Vasmatzis, Nikolaos Xu, Hang Kim, Minsoo Bockol, Matthew O’Brien, Daniel Grill, Diane Warner, Nathaniel Munoz-Gomez, Miguel Kossick, Kimberlee Johnson, Ruth Mouchli, Mohamad Felmlee-Devine, Donna Washechek-Aletto, Jill Smyrk, Thomas Oberg, Ann Wang, Junwen Chia, Nicholas Abyzov, Alexej Ahlquist, David Boardman, Lisa A. Molecular characterization of colorectal adenomas with and without malignancy reveals distinguishing genome, transcriptome and methylome alterations |
title | Molecular characterization of colorectal adenomas with and without malignancy reveals distinguishing genome, transcriptome and methylome alterations |
title_full | Molecular characterization of colorectal adenomas with and without malignancy reveals distinguishing genome, transcriptome and methylome alterations |
title_fullStr | Molecular characterization of colorectal adenomas with and without malignancy reveals distinguishing genome, transcriptome and methylome alterations |
title_full_unstemmed | Molecular characterization of colorectal adenomas with and without malignancy reveals distinguishing genome, transcriptome and methylome alterations |
title_short | Molecular characterization of colorectal adenomas with and without malignancy reveals distinguishing genome, transcriptome and methylome alterations |
title_sort | molecular characterization of colorectal adenomas with and without malignancy reveals distinguishing genome, transcriptome and methylome alterations |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5816667/ https://www.ncbi.nlm.nih.gov/pubmed/29453410 http://dx.doi.org/10.1038/s41598-018-21525-4 |
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