Amplification and overexpression of the cyclin D1 and epidermal growth factor receptor genes in non-small-cell lung cancer
Amplification and overexpression of the cyclin D1 and epidermal growth factor receptor genes in non-small-cell lung cancer
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DOI：
10.1007/s004320050243
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发表时间：
1999-02-01
影响因子：
3.6
通讯作者：
Salmon, DJ
中科院分区：
文献类型：
--
作者：
Reissmann, PT;Koga, H;Salmon, DJ
目的：研究298例非小细胞肺癌（NSCLC）标本中细胞周期蛋白D1和表皮生长因子受体（EGFR）基因的结构和表达。方法：采用Southern杂交分析基因结构，北方杂交分析和免疫组化分析基因表达。结果：298例标本中有14例（5%）出现细胞周期蛋白D1基因扩增。所有12/12的标本与扩增的细胞周期蛋白D1基因的RNA可被发现表达细胞周期蛋白D1的转录本，和11/12的转录本过表达的水平高于未参与肺。EGFR基因在17/286份检测的NSCLC样本中扩增，在22/169（13%）例检测病例中过表达，包括12/13例基因扩增（RNA可用）的病例。细胞周期蛋白D1基因扩增与晚期淋巴结转移相关（P = 0.043），但与较大的肿瘤大小或不良结局无关。细胞周期蛋白D1基因扩增和过表达的发生与视网膜母细胞瘤肿瘤抑制基因（RB）失活无关，但细胞周期蛋白D1基因扩增的肿瘤更可能有EGFR基因扩增（P < 0.005）。EGFR基因扩增或过表达与肿瘤大小、淋巴结受累、患者人口统计学数据或生存率无关。结论：这些数据表明，细胞周期蛋白D1和EGFR基因扩增和过表达的NSCLC，细胞周期蛋白D1基因的扩增经常发生与EGFR基因的扩增。
Purpose: To study the structure and expression of the cyclin D1 and the epidermal growth factor receptor (EGFR) genes in a cohort of 298 non-small-cell lung cancer (NSCLC) specimens. Methods: Gene structure was studied by Southern analysis, and gene expression was studied by Northern analysis and immunohistochemical analysis. Results: Amplification of the cyclin D1 locus was found in 14/298 (5%) specimens. All 12/12 specimens with amplification of the cyclin D1 gene for which RNA was available were found to express the cyclin D1 transcript, and 11/12 overexpressed the transcript to levels higher than that of uninvolved lung. The EGFR gene was amplified in 17/286 samples of NSCLC tested, and was overexpressed in 22/169 (13%) cases tested, including 12/13 cases with amplification of the gene for which RNA was available. Cyclin D1 gene amplification was associated with advanced lymph node involvement (P = 0.043), but not with larger tumor size or adverse outcome. Cyclin D1 gene amplification and overexpression occurred independently of retinoblastoma tumor-suppressor gene (RB) inactivation, but tumors with amplification of the cyclin D1 gene were more likely to have EGFR gene amplification (P < 0.005). No correlation of EGFR gene amplification or overexpression with tumor size, lymph node involvement, patient demographic data, or survival was identified. Conclusions: These data indicate that the cyclin D1 and EGFR genes are amplified and overexpressed in NSCLC, and amplification of the cyclin D1 gene occurs frequently in conjunction with amplification of the EGFR gene.