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FBXW7 missense mutation: a novel negative prognostic factor in metastatic colorectal adenocarcinoma
BACKGROUND: FBXW7 functions as a ubiquitin ligase tagging multiple dominant oncogenic proteins and commonly mutates in colorectal cancer. Data suggest missense mutations lead to greater loss of FBXW7 function than other gene aberrations do. However, the clinicopathologic factors and outcomes associa...
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/PMC5503612/ https://www.ncbi.nlm.nih.gov/pubmed/28424412 http://dx.doi.org/10.18632/oncotarget.16848 |
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author | Korphaisarn, Krittiya Morris, Van Karlyle Overman, Michael J. Fogelman, David R. Kee, Bryan K. Kanwal Pratap Singh, Raghav Manuel, Shanequa Shureiqi, Imad Wolff, Robert A. Eng, Cathy Menter, David Hamilton, Stanley R. Kopetz, Scott Dasari, Arvind |
author_facet | Korphaisarn, Krittiya Morris, Van Karlyle Overman, Michael J. Fogelman, David R. Kee, Bryan K. Kanwal Pratap Singh, Raghav Manuel, Shanequa Shureiqi, Imad Wolff, Robert A. Eng, Cathy Menter, David Hamilton, Stanley R. Kopetz, Scott Dasari, Arvind |
author_sort | Korphaisarn, Krittiya |
collection | PubMed |
description | BACKGROUND: FBXW7 functions as a ubiquitin ligase tagging multiple dominant oncogenic proteins and commonly mutates in colorectal cancer. Data suggest missense mutations lead to greater loss of FBXW7 function than other gene aberrations do. However, the clinicopathologic factors and outcomes associated with FBXW7 missense mutations in metastatic colorectal cancer (mCRC) have not been described. METHODS: Data were obtained from mCRC patients whose tumors were evaluated by next-generation sequencing for hotspot mutations at The University of Texas MD Anderson Cancer Center. Alterations in FBXW7 were identified, and their associations with clinicopathologic features and overall survival (OS) were evaluated. RESULTS: Of 855 mCRC patients, 571 had data on FBXW7 status; 43 (7.5%) had FBXW7 mutations, including 37 with missense mutations. R465C mutations in exon 9 were the most common missense mutations (18.6%). PIK3CA mutations were associated with FBXW7 missense mutations (p=0.012). On univariate analysis, patients with FBXW7 missense mutations had significantly worse OS (median 28.7 mo) than those with wild-type FBXW7 (median 46.6 mo; p=0.003). On multivariate analysis including other known prognostic factors such as BRAF mutations, FBXW7 missense mutations were the strongest negative prognostic factor for OS (hazard ratio 2.0; p=0.003). CONCLUSIONS: In the largest clinical dataset of mCRC to date, FBXW7 missense mutations showed a strong negative prognostic association. |
format | Online Article Text |
id | pubmed-5503612 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-55036122017-07-11 FBXW7 missense mutation: a novel negative prognostic factor in metastatic colorectal adenocarcinoma Korphaisarn, Krittiya Morris, Van Karlyle Overman, Michael J. Fogelman, David R. Kee, Bryan K. Kanwal Pratap Singh, Raghav Manuel, Shanequa Shureiqi, Imad Wolff, Robert A. Eng, Cathy Menter, David Hamilton, Stanley R. Kopetz, Scott Dasari, Arvind Oncotarget Research Paper BACKGROUND: FBXW7 functions as a ubiquitin ligase tagging multiple dominant oncogenic proteins and commonly mutates in colorectal cancer. Data suggest missense mutations lead to greater loss of FBXW7 function than other gene aberrations do. However, the clinicopathologic factors and outcomes associated with FBXW7 missense mutations in metastatic colorectal cancer (mCRC) have not been described. METHODS: Data were obtained from mCRC patients whose tumors were evaluated by next-generation sequencing for hotspot mutations at The University of Texas MD Anderson Cancer Center. Alterations in FBXW7 were identified, and their associations with clinicopathologic features and overall survival (OS) were evaluated. RESULTS: Of 855 mCRC patients, 571 had data on FBXW7 status; 43 (7.5%) had FBXW7 mutations, including 37 with missense mutations. R465C mutations in exon 9 were the most common missense mutations (18.6%). PIK3CA mutations were associated with FBXW7 missense mutations (p=0.012). On univariate analysis, patients with FBXW7 missense mutations had significantly worse OS (median 28.7 mo) than those with wild-type FBXW7 (median 46.6 mo; p=0.003). On multivariate analysis including other known prognostic factors such as BRAF mutations, FBXW7 missense mutations were the strongest negative prognostic factor for OS (hazard ratio 2.0; p=0.003). CONCLUSIONS: In the largest clinical dataset of mCRC to date, FBXW7 missense mutations showed a strong negative prognostic association. Impact Journals LLC 2017-04-05 /pmc/articles/PMC5503612/ /pubmed/28424412 http://dx.doi.org/10.18632/oncotarget.16848 Text en Copyright: © 2017 Korphaisarn et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Korphaisarn, Krittiya Morris, Van Karlyle Overman, Michael J. Fogelman, David R. Kee, Bryan K. Kanwal Pratap Singh, Raghav Manuel, Shanequa Shureiqi, Imad Wolff, Robert A. Eng, Cathy Menter, David Hamilton, Stanley R. Kopetz, Scott Dasari, Arvind FBXW7 missense mutation: a novel negative prognostic factor in metastatic colorectal adenocarcinoma |
title | FBXW7 missense mutation: a novel negative prognostic factor in metastatic colorectal adenocarcinoma |
title_full | FBXW7 missense mutation: a novel negative prognostic factor in metastatic colorectal adenocarcinoma |
title_fullStr | FBXW7 missense mutation: a novel negative prognostic factor in metastatic colorectal adenocarcinoma |
title_full_unstemmed | FBXW7 missense mutation: a novel negative prognostic factor in metastatic colorectal adenocarcinoma |
title_short | FBXW7 missense mutation: a novel negative prognostic factor in metastatic colorectal adenocarcinoma |
title_sort | fbxw7 missense mutation: a novel negative prognostic factor in metastatic colorectal adenocarcinoma |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5503612/ https://www.ncbi.nlm.nih.gov/pubmed/28424412 http://dx.doi.org/10.18632/oncotarget.16848 |
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