The gene ratios c-MYC:cyclin-dependent kinase (CDK)N2A and CCND1:CDKN2A correlate with poor prognosis in squamous cell carcinoma of the head and neck.
The gene ratios c-MYC:cyclin-dependent kinase (CDK)N2A and CCND1:CDKN2A correlate with poor prognosis in squamous cell carcinoma of the head and neck.
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发表时间：
2003-05
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通讯作者：
J. Akervall;U. Bockmühl;I. Petersen;Kun-Qing Yang;T. Carey;D. Kurnit
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作者：
J. Akervall;U. Bockmühl;I. Petersen;Kun-Qing Yang;T. Carey;D. Kurnit
目的肿瘤-淋巴结-转移分类不能完全预测头颈部鳞状细胞癌患者的治疗结果和预后。有人建议使用不同的生物标志物来产生额外的预后信息，但迄今为止尚未将单一标志物引入临床。本研究的目的是分析经常扩增的癌基因 CCND1 和 c-MYC 与常见缺失的抑癌基因细胞周期蛋白依赖性激酶 (CDK)N2A (p16) 的拷贝数，以增强临床意义。实验设计 使用 c-MYC、CCND1 和 CDKN2A 的特异性引物，通过实时 PCR 分析从 78 名未经治疗的患者的诊断活检中提取的 DNA。通过将 c-MYC 或 CCND1 的拷贝数除以 CDKN2A 来计算基因拷贝数比率。比率> 2 被定义为增强。这些数据与无病间隔和疾病特异性生存相关。结果 78 例中有 35 例 (45%) 检测到 c-MYC:CDKN2A 基因比例增强，78 例中有 36 例 (46%) 检测到 CCND1:CDKN2A 基因比例增强。 c-MYC:CDKN2A 和 CCND1:CDKN2A 比率与相对于死亡的疾病特异性生存率相关（P 分别 = 0.042 和 0.049；对数秩检验）。此外，c-MYC:CDKN2A 的增强与较短的无病间隔相关，表现为复发或转移的发生（P = 0.014；对数秩检验）。结论 我们得出的结论是，与单一遗传畸变分析相比，CCND1 和/或 c-MYC 扩增与 CDKN2A 缺失相结合可产生额外的预后信息。这些基因比率通过诊断活检的实时 PCR 等敏感方法进行分析，可能有助于临床医生对头颈部鳞状细胞癌进行个体化治疗，因为它们反映了肿瘤的生物学特性。这可以用作肿瘤-淋巴结-转移分类系统的辅助。
PURPOSE Tumor-Node-Metastasis classification does not fully predict outcome of treatment and prognosis in patients with squamous cell carcinoma of the head and neck. Different biomarkers have been suggested to yield additional prognostic information, but no single marker has thus far been introduced in the clinic. The objective of the present study was to analyze the copy number of the frequently amplified oncogenes CCND1 and c-MYC in relation to the commonly deleted tumor suppressor gene cyclin-dependent kinase (CDK)N2A (p16) to enhance the clinical significance. EXPERIMENTAL DESIGN Extracted DNA from diagnostic biopsies of 78 untreated patients were analyzed by real-time PCR with specific primers for c-MYC, CCND1, and CDKN2A. Gene copy number ratios were calculated by dividing the copy number of c-MYC or CCND1 with CDKN2A. Ratios > 2 were defined as enhanced. These data were related to disease-free interval and disease-specific survival. RESULTS Enhanced gene ratio of c-MYC:CDKN2A was detected in 35 of 78 (45%) and enhanced ratio of CCND1:CDKN2A in 36 of 78 (46%) of the cases. The c-MYC:CDKN2A and CCND1:CDKN2A ratios correlated with disease-specific survival with respect to death (P = 0.042 and 0.049, respectively; Log-rank test). Furthermore, enhancement of c-MYC:CDKN2A was associated with a shorter disease-free interval as marked by the development of recurrences or metastases (P = 0.014; Log-rank test). CONCLUSIONS We conclude that CCND1 and/or c-MYC amplification, when combined with CDKN2A deletion, yield additional prognostic information as compared with analysis of single genetic aberrations. These gene ratios, as analyzed by a sensitive method like real-time PCR on diagnostic biopsies, might help clinicians to individualize the treatment of squamous cell carcinoma of the head and neck as they reflect the biological properties of the tumors. This could be used as an adjunct to the Tumor-Node-Metastasis classification system.