title: Cyclin alterations in diverse cancers: Outcome and co-amplification network.
abstract: 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.
authors.affiliation: Center for Personalized Cancer Therapy, and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Schwaederlé
authors.affiliation: Center for Personalized Cancer Therapy, and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Daniels
authors.affiliation: Center for Personalized Cancer Therapy, and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Piccioni
authors.affiliation: Center for Personalized Cancer Therapy, and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, USA.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Fanta
authors.affiliation: Center for Personalized Cancer Therapy, and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Schwab
authors.affiliation: Center for Personalized Cancer Therapy, and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Shimabukuro
authors.affiliation: Center for Personalized Cancer Therapy, and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, USA.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Parker
authors.affiliation: Center for Personalized Cancer Therapy, and Division of Hematology and Oncology, UCSD Moores Cancer Center, La Jolla, USA.
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016017:Odds Ratio; D010641:Phenotype; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D016213:Cyclins