Cyclin alterations in diverse cancers: Outcome and co-amplification network. Oncotarget 2015 Feb 20;6(5):3033-42
Date
01/19/2015Pubmed ID
25596748Pubmed Central ID
PMC4413635DOI
10.18632/oncotarget.2848Scopus ID
2-s2.0-84923294701 (requires institutional sign-in at Scopus site) 30 CitationsAbstract
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.
Author List
Schwaederlé M, Daniels GA, Piccioni DE, Fanta PT, Schwab RB, Shimabukuro KA, Parker BA, Kurzrock RAuthor
Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Biomarkers, TumorCyclins
Disease-Free Survival
Female
Gene Amplification
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Genetic Predisposition to Disease
Humans
Kaplan-Meier Estimate
Logistic Models
Male
Middle Aged
Multivariate Analysis
Neoplasm Metastasis
Neoplasm Recurrence, Local
Neoplasms
Odds Ratio
Phenotype
Proportional Hazards Models
Retrospective Studies
Risk Factors
Time Factors
