Recurrent Amplification at 7q21.2 Targets CDK6 Gene in Primary Myxofibrosarcomas and Identifies CDK6 Overexpression as an Independent Adverse Prognosticator
Jen-Wei Tsai, Yu-Chien Kao, Chien-Feng Li, Hsuan-Ying Huang. E-Da Hospital, Kaohsiung, Taiwan; Wan Fang Hospital, Taipei, Taiwan; Chi Mei Medical Center, Tainan, Taiwan; Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
Background: Myxofibrosarcoma is genetically complex and remains obscure in molecular determinants of clinical aggressiveness. Our prior array comparative genomic hybridization study on myxofibrosarcomas revealed recurrent gains of 7q where CDK6 gene displayed increased DNA copies.
Design: On tissue microarrays, CDK6 immunoexpression was assessable in 77 primary tumors, 55 of which were successfully determined for CDK6 gene dosage by real-time PCR using genomic DNA extracted from laser-microdissected tumor cells. Gene status and protein expression of CDK6 were correlated with each other, clincopathological variables, metastasis-free survival (MFS), and disease-specific survival (DSS).
Results: Detected in 21(27.2%) of 77 and 13(23.6%) of 55 cases, respectively, protein overexpression and gene amplification of CDK6 were highly related to each other (p<0.001) and associated with higher grades (overexpression, p=0.004; amplification, p=0.014). Univariately, both protein overexpression (MFS, p=0.0002; DSS, p=0.0015) and gene amplification (MFS, p=0.0001; DSS, p=0.0083) were significantly associated with worse outcomes. Importantly, CDK6 overexpression independently portended poorer MFS (p=0.0015, risk ratio [RR] =7.411) and also inferior DSS (p=0.0069, RR =6.006).
Conclusions: In approximately a quarter of primary myxofibrosarcomas, CDK6 overexpression is mostly driven by gene amplification on 7q, associated with adverse prognosticators, and independently predictive of worse outcomes, highlighting its possible causative role in tumor aggressiveness.
Category: Bone & Soft Tissue
Monday, March 19, 2012 1:00 PM
Poster Session II # 17, Monday Afternoon