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Mucinous Adenocarcinoma of the Rectum: A Whole Genome Sequencing Study
INTRODUCTION: Mucinous adenocarcinoma of the rectum is an infrequently encountered histological subtype that is associated with an impaired response to chemoradiotherapy and a worse overall prognosis. A genomic profile analysis of mucinous rectal tumors has not yet been performed. The aim of this st...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479243/ https://www.ncbi.nlm.nih.gov/pubmed/32984045 http://dx.doi.org/10.3389/fonc.2020.01682 |
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author | Reynolds, Ian S. Thomas, Valentina O’Connell, Emer Fichtner, Michael McNamara, Deborah A. Kay, Elaine W. Prehn, Jochen H. M. Burke, John P. Furney, Simon J. |
author_facet | Reynolds, Ian S. Thomas, Valentina O’Connell, Emer Fichtner, Michael McNamara, Deborah A. Kay, Elaine W. Prehn, Jochen H. M. Burke, John P. Furney, Simon J. |
author_sort | Reynolds, Ian S. |
collection | PubMed |
description | INTRODUCTION: Mucinous adenocarcinoma of the rectum is an infrequently encountered histological subtype that is associated with an impaired response to chemoradiotherapy and a worse overall prognosis. A genomic profile analysis of mucinous rectal tumors has not yet been performed. The aim of this study was to comprehensively describe the burden of somatic mutations and copy number variation as well as perform mutational signature and microbial analysis of an in-house collected cohort of mucinous adenocarcinoma of the rectum. METHODS: Genomic DNA was extracted from 10 cases of mucinous rectal cancer and matched normal tissue. Whole genome sequencing (WGS) was carried out on these 10 cases and a comprehensive bioinformatic analysis was undertaken. RESULTS: The average number of SNVs, InDels and SVs in the cohort was 16,600, 1,855, and 120, respectively. A single case was MSI-H. KRAS mutations were found in 70% of cases while TP53 was mutated in only 40% of cases. CNA gain was identified on chromosomes 7, 8, 12, 13, and 20 while CNA loss was found on chromosomes 4, 8, 17, and 18 corresponding to oncogenes and tumor suppressor genes, respectively. Overall mucinous rectal cancers are more likely to be MSI-H and to have KRAS, BRAF, and PIK3CA mutations when compared to rectal adenocarcinoma NOS. Microbial analysis demonstrated an abundance of Fusobacterium nucleatum in tumor samples compared to normal tissue. CONCLUSION: This study provides a detailed WGS analysis of 10 cases of mucinous rectal cancer. It demonstrates an important lesson in tumor biology in that histologically similar tumors can have extensive differences at the genomic level. This study is relevant as it raises important questions about the relationship between bacteria and malignancy. |
format | Online Article Text |
id | pubmed-7479243 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74792432020-09-26 Mucinous Adenocarcinoma of the Rectum: A Whole Genome Sequencing Study Reynolds, Ian S. Thomas, Valentina O’Connell, Emer Fichtner, Michael McNamara, Deborah A. Kay, Elaine W. Prehn, Jochen H. M. Burke, John P. Furney, Simon J. Front Oncol Oncology INTRODUCTION: Mucinous adenocarcinoma of the rectum is an infrequently encountered histological subtype that is associated with an impaired response to chemoradiotherapy and a worse overall prognosis. A genomic profile analysis of mucinous rectal tumors has not yet been performed. The aim of this study was to comprehensively describe the burden of somatic mutations and copy number variation as well as perform mutational signature and microbial analysis of an in-house collected cohort of mucinous adenocarcinoma of the rectum. METHODS: Genomic DNA was extracted from 10 cases of mucinous rectal cancer and matched normal tissue. Whole genome sequencing (WGS) was carried out on these 10 cases and a comprehensive bioinformatic analysis was undertaken. RESULTS: The average number of SNVs, InDels and SVs in the cohort was 16,600, 1,855, and 120, respectively. A single case was MSI-H. KRAS mutations were found in 70% of cases while TP53 was mutated in only 40% of cases. CNA gain was identified on chromosomes 7, 8, 12, 13, and 20 while CNA loss was found on chromosomes 4, 8, 17, and 18 corresponding to oncogenes and tumor suppressor genes, respectively. Overall mucinous rectal cancers are more likely to be MSI-H and to have KRAS, BRAF, and PIK3CA mutations when compared to rectal adenocarcinoma NOS. Microbial analysis demonstrated an abundance of Fusobacterium nucleatum in tumor samples compared to normal tissue. CONCLUSION: This study provides a detailed WGS analysis of 10 cases of mucinous rectal cancer. It demonstrates an important lesson in tumor biology in that histologically similar tumors can have extensive differences at the genomic level. This study is relevant as it raises important questions about the relationship between bacteria and malignancy. Frontiers Media S.A. 2020-08-26 /pmc/articles/PMC7479243/ /pubmed/32984045 http://dx.doi.org/10.3389/fonc.2020.01682 Text en Copyright © 2020 Reynolds, Thomas, O’Connell, Fichtner, McNamara, Kay, Prehn, Burke and Furney. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Reynolds, Ian S. Thomas, Valentina O’Connell, Emer Fichtner, Michael McNamara, Deborah A. Kay, Elaine W. Prehn, Jochen H. M. Burke, John P. Furney, Simon J. Mucinous Adenocarcinoma of the Rectum: A Whole Genome Sequencing Study |
title | Mucinous Adenocarcinoma of the Rectum: A Whole Genome Sequencing Study |
title_full | Mucinous Adenocarcinoma of the Rectum: A Whole Genome Sequencing Study |
title_fullStr | Mucinous Adenocarcinoma of the Rectum: A Whole Genome Sequencing Study |
title_full_unstemmed | Mucinous Adenocarcinoma of the Rectum: A Whole Genome Sequencing Study |
title_short | Mucinous Adenocarcinoma of the Rectum: A Whole Genome Sequencing Study |
title_sort | mucinous adenocarcinoma of the rectum: a whole genome sequencing study |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479243/ https://www.ncbi.nlm.nih.gov/pubmed/32984045 http://dx.doi.org/10.3389/fonc.2020.01682 |
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