Cargando…

Cyclin alterations in diverse cancers: outcome and co-amplification network

Cyclin genes are key regulatory components of the cell cycle. With the development of new agents, cyclin-related genes are becoming increasingly important as they can be targeted. Yet, the biological implications of these alterations have not been fully studied. Clinical characteristics and outcome...

Descripción completa

Detalles Bibliográficos
Autores principales: Schwaederlé, Maria, Daniels, Gregory A., Piccioni, David E., Fanta, Paul T., Schwab, Richard B., Shimabukuro, Kelly A., Parker, Barbara A., Kurzrock, Razelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413635/
https://www.ncbi.nlm.nih.gov/pubmed/25596748
_version_ 1782368811797708800
author Schwaederlé, Maria
Daniels, Gregory A.
Piccioni, David E.
Fanta, Paul T.
Schwab, Richard B.
Shimabukuro, Kelly A.
Parker, Barbara A.
Kurzrock, Razelle
author_facet Schwaederlé, Maria
Daniels, Gregory A.
Piccioni, David E.
Fanta, Paul T.
Schwab, Richard B.
Shimabukuro, Kelly A.
Parker, Barbara A.
Kurzrock, Razelle
author_sort Schwaederlé, Maria
collection PubMed
description Cyclin genes are key regulatory components of the cell cycle. With the development of new agents, cyclin-related genes are becoming increasingly important as they can be targeted. Yet, the biological implications of these alterations have not been fully studied. Clinical characteristics and outcome parameters were compared for patients harboring cyclin alterations versus not. CCN alterations were found in 13% of our population (50/392; all amplifications) and were associated with breast cancer (P < 0.0001), a higher median number of concomitant molecular alterations (P < 0.0001), and liver metastases (P = 0.046). Harboring a cyclin amplification was not associated with overall survival, the time to metastasis/recurrence, nor with the best progression-free survival. In a Cox regression model, gastrointestinal histology (P < 0.0001), PTEN (P < 0.0001), and CDK alterations (P = 0.041) had a significant association with poorer overall survival. CCN amplifications significantly correlated with alterations in FGF/FGFR family genes as well as in MET and ARFRP1. An extended correlation study shed light on a network of co-amplifications influenced in part by genes that were localized on the same amplicons. CCN amplifications are common across cancers and had distinctive biological associations. Customized combinations targeting the cyclin pathway as well as the extended co-amplification network may be necessary in order to address resistance mechanisms.
format Online
Article
Text
id pubmed-4413635
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Impact Journals LLC
record_format MEDLINE/PubMed
spelling pubmed-44136352015-05-08 Cyclin alterations in diverse cancers: outcome and co-amplification network Schwaederlé, Maria Daniels, Gregory A. Piccioni, David E. Fanta, Paul T. Schwab, Richard B. Shimabukuro, Kelly A. Parker, Barbara A. Kurzrock, Razelle Oncotarget Research Paper Cyclin genes are key regulatory components of the cell cycle. With the development of new agents, cyclin-related genes are becoming increasingly important as they can be targeted. Yet, the biological implications of these alterations have not been fully studied. Clinical characteristics and outcome parameters were compared for patients harboring cyclin alterations versus not. CCN alterations were found in 13% of our population (50/392; all amplifications) and were associated with breast cancer (P < 0.0001), a higher median number of concomitant molecular alterations (P < 0.0001), and liver metastases (P = 0.046). Harboring a cyclin amplification was not associated with overall survival, the time to metastasis/recurrence, nor with the best progression-free survival. In a Cox regression model, gastrointestinal histology (P < 0.0001), PTEN (P < 0.0001), and CDK alterations (P = 0.041) had a significant association with poorer overall survival. CCN amplifications significantly correlated with alterations in FGF/FGFR family genes as well as in MET and ARFRP1. An extended correlation study shed light on a network of co-amplifications influenced in part by genes that were localized on the same amplicons. CCN amplifications are common across cancers and had distinctive biological associations. Customized combinations targeting the cyclin pathway as well as the extended co-amplification network may be necessary in order to address resistance mechanisms. Impact Journals LLC 2014-12-18 /pmc/articles/PMC4413635/ /pubmed/25596748 Text en Copyright: © 2015 Schwaederlé 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
Schwaederlé, Maria
Daniels, Gregory A.
Piccioni, David E.
Fanta, Paul T.
Schwab, Richard B.
Shimabukuro, Kelly A.
Parker, Barbara A.
Kurzrock, Razelle
Cyclin alterations in diverse cancers: outcome and co-amplification network
title Cyclin alterations in diverse cancers: outcome and co-amplification network
title_full Cyclin alterations in diverse cancers: outcome and co-amplification network
title_fullStr Cyclin alterations in diverse cancers: outcome and co-amplification network
title_full_unstemmed Cyclin alterations in diverse cancers: outcome and co-amplification network
title_short Cyclin alterations in diverse cancers: outcome and co-amplification network
title_sort cyclin alterations in diverse cancers: outcome and co-amplification network
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413635/
https://www.ncbi.nlm.nih.gov/pubmed/25596748
work_keys_str_mv AT schwaederlemaria cyclinalterationsindiversecancersoutcomeandcoamplificationnetwork
AT danielsgregorya cyclinalterationsindiversecancersoutcomeandcoamplificationnetwork
AT piccionidavide cyclinalterationsindiversecancersoutcomeandcoamplificationnetwork
AT fantapault cyclinalterationsindiversecancersoutcomeandcoamplificationnetwork
AT schwabrichardb cyclinalterationsindiversecancersoutcomeandcoamplificationnetwork
AT shimabukurokellya cyclinalterationsindiversecancersoutcomeandcoamplificationnetwork
AT parkerbarbaraa cyclinalterationsindiversecancersoutcomeandcoamplificationnetwork
AT kurzrockrazelle cyclinalterationsindiversecancersoutcomeandcoamplificationnetwork