國家衛生研究院 NHRI:Item 3990099045/6374
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    題名: Recurrent Amplification at 7q21.2 Targets CDK6 Gene in Primary Myxofibrosarcomas and Identifies CDK6 Overexpression as an Independent Adverse Prognosticator
    作者: Tsai, JW;Li, CF;Kao, YC;Wang, JW;Fang, FM;Wang, YH;Wu, WR;Wu, LC;Hsing, CH;Li, SH;Yu, SC;Lan, J;Huang, HY
    貢獻者: National Institute of Cancer Research
    摘要: Background. Myxofibrosarcoma is genetically complexand remains obscure in molecular determinants of clinicalaggressiveness. Our prior study revealed recurrent gains of 7qin myxofibrosarcomas where MET and CDK6 genes displayedincreased DNA copies. Previously, we demonstrated theimplication of MET overexpression, prompting us to furtherelucidate the roles of CDK6 in myxo?brosarcomas.Materials. On tissue microarrays, CDK6 immunoexpres-sion was assessable in 77 primary tumors, 55 of whichwere successfully quantified for CDK6 and MET genes byreal-time PCR using genomic DNA extracted from laser-microdissected tumor cells. Gene status and proteinexpression of CDK6 were correlated with each other,clinicopathological variables, metastasis-free survival(MFS), and disease-specific survival (DSS).Results. Protein overexpression and gene amplification ofCDK6, which were detected in 21 of 77 (27.2 %) and 13 of55 cases (23.6 %), respectively, were highly related to eachother (p \ .001) and associated with higher grades (over-expression, p = .004; amplification, p = .014). There wasa strong correlation between CDK6 and MET gene copies(p \ .001, r = 0.0714). Importantly, CDK6 protein over-expression (MFS, p = .0002; DSS, p = .0015) and geneamplifocation (MFS, p = .0001; DSS, p = .0083) wereboth univariately associated with worse outcomes. Toge-ther with nonextremity location and AJCC stage IIIdisease, CDK6 overexpression independently portendedinferior MFS (p = .0015, risk ratio [RR] = 7.411). Thisaberration, along with nonextremity location, was also anindependent adverse prognosticator of DSS (p = .0069,RR = 6.006).Conclusions. In approximately a quarter of primarymyxofibrosarcomas, CDK6 overexpression is mostly dri-ven by gene amplification on 7q, associated with adverseprognosticators, and independently predictive of worseoutcomes, highlighting its possible causative role in tumoraggressiveness.
    日期: 2012-08
    關聯: Annals of Surgical Oncology. 2012 Aug;19(8):2716-2725.
    Link to: http://dx.doi.org/10.1245/s10434-012-2317-3
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1068-9265&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000306789000041
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84864992498
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