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Comparative molecular analyses of left-sided colon, right-sided colon, and rectal cancers
Tumor sidedness has emerged as an important prognostic and predictive factor in the treatment of colorectal cancer. Recent studies demonstrate that patients with advanced right-sided colon cancers have a worse prognosis than those with left-sided colon or rectal cancers, and these patient subgroups...
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/PMC5689690/ https://www.ncbi.nlm.nih.gov/pubmed/29156800 http://dx.doi.org/10.18632/oncotarget.21169 |
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author | Salem, Mohamed E. Weinberg, Benjamin A. Xiu, Joanne El-Deiry, Wafik S. Hwang, Jimmy J. Gatalica, Zoran Philip, Philip A. Shields, Anthony F. Lenz, Heinz-Josef Marshall, John L. |
author_facet | Salem, Mohamed E. Weinberg, Benjamin A. Xiu, Joanne El-Deiry, Wafik S. Hwang, Jimmy J. Gatalica, Zoran Philip, Philip A. Shields, Anthony F. Lenz, Heinz-Josef Marshall, John L. |
author_sort | Salem, Mohamed E. |
collection | PubMed |
description | Tumor sidedness has emerged as an important prognostic and predictive factor in the treatment of colorectal cancer. Recent studies demonstrate that patients with advanced right-sided colon cancers have a worse prognosis than those with left-sided colon or rectal cancers, and these patient subgroups respond differently to biological therapies. Historically, management of patients with metastatic colon and rectal cancers has been similar, and colon and rectal cancer patients have been grouped together in large clinical trials. Clearly, the differences in molecular biology among right-sided colon, left-sided colon, and rectal cancers should be further studied in order to account for disparities in clinical outcomes. We profiled 10,570 colorectal tumors (of which 2,413 were identified as arising from the left colon, right colon, or rectum) using next-generation sequencing, immunohistochemistry, chromogenic in-situ hybridization, and fragment analysis (Caris Life Sciences, Phoenix, AZ). Right-sided colon cancers had higher rates of microsatellite instability, more frequent aberrant activation of the EGFR pathway including higher BRAF and PIK3CA mutation rates, and increased mutational burden compared to left-sided colon and rectal cancers. Rectal cancers had higher rates of TOPO1 expression and Her2/neu amplification compared to both left- and right-sided colon cancers. Molecular variations among right-sided colon, left-sided colon, and rectal tumors may contribute to differences in clinical behavior. The site of tumor origin (left colon, right colon, or rectum) should certainly be considered when selecting treatment regimens and stratifying patients for future clinical trials. |
format | Online Article Text |
id | pubmed-5689690 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-56896902017-11-17 Comparative molecular analyses of left-sided colon, right-sided colon, and rectal cancers Salem, Mohamed E. Weinberg, Benjamin A. Xiu, Joanne El-Deiry, Wafik S. Hwang, Jimmy J. Gatalica, Zoran Philip, Philip A. Shields, Anthony F. Lenz, Heinz-Josef Marshall, John L. Oncotarget Research Paper Tumor sidedness has emerged as an important prognostic and predictive factor in the treatment of colorectal cancer. Recent studies demonstrate that patients with advanced right-sided colon cancers have a worse prognosis than those with left-sided colon or rectal cancers, and these patient subgroups respond differently to biological therapies. Historically, management of patients with metastatic colon and rectal cancers has been similar, and colon and rectal cancer patients have been grouped together in large clinical trials. Clearly, the differences in molecular biology among right-sided colon, left-sided colon, and rectal cancers should be further studied in order to account for disparities in clinical outcomes. We profiled 10,570 colorectal tumors (of which 2,413 were identified as arising from the left colon, right colon, or rectum) using next-generation sequencing, immunohistochemistry, chromogenic in-situ hybridization, and fragment analysis (Caris Life Sciences, Phoenix, AZ). Right-sided colon cancers had higher rates of microsatellite instability, more frequent aberrant activation of the EGFR pathway including higher BRAF and PIK3CA mutation rates, and increased mutational burden compared to left-sided colon and rectal cancers. Rectal cancers had higher rates of TOPO1 expression and Her2/neu amplification compared to both left- and right-sided colon cancers. Molecular variations among right-sided colon, left-sided colon, and rectal tumors may contribute to differences in clinical behavior. The site of tumor origin (left colon, right colon, or rectum) should certainly be considered when selecting treatment regimens and stratifying patients for future clinical trials. Impact Journals LLC 2017-09-21 /pmc/articles/PMC5689690/ /pubmed/29156800 http://dx.doi.org/10.18632/oncotarget.21169 Text en Copyright: © 2017 Salem 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 (http://creativecommons.org/licenses/by/3.0/) 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 Salem, Mohamed E. Weinberg, Benjamin A. Xiu, Joanne El-Deiry, Wafik S. Hwang, Jimmy J. Gatalica, Zoran Philip, Philip A. Shields, Anthony F. Lenz, Heinz-Josef Marshall, John L. Comparative molecular analyses of left-sided colon, right-sided colon, and rectal cancers |
title | Comparative molecular analyses of left-sided colon, right-sided colon, and rectal cancers |
title_full | Comparative molecular analyses of left-sided colon, right-sided colon, and rectal cancers |
title_fullStr | Comparative molecular analyses of left-sided colon, right-sided colon, and rectal cancers |
title_full_unstemmed | Comparative molecular analyses of left-sided colon, right-sided colon, and rectal cancers |
title_short | Comparative molecular analyses of left-sided colon, right-sided colon, and rectal cancers |
title_sort | comparative molecular analyses of left-sided colon, right-sided colon, and rectal cancers |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5689690/ https://www.ncbi.nlm.nih.gov/pubmed/29156800 http://dx.doi.org/10.18632/oncotarget.21169 |
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