Cyclin alterations in diverse cancers: Outcome and co-amplification network
Metrics: PDF 2066 views | HTML 3226 views | ?
Maria Schwaederlé1, Gregory A. Daniels1, David E. Piccioni1, Paul T. Fanta1, Richard B. Schwab1, Kelly A. Shimabukuro1, Barbara A. Parker1, Razelle Kurzrock1
1Center for Personalized Cancer Therapy, and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, USA
Maria Schwaederlé, e-mail: [email protected]
Keywords: cyclin, next generation sequencing, molecular profile, amplification, Cancer
Received: October 03, 2014 Accepted: December 05, 2014 Published: December 18, 2014
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.