Inactivation of the retinoblastoma susceptibility gene in non-small-cell lung cancer. The Lung Cancer Study Group.
Inactivation of the retinoblastoma susceptibility gene in non-small-cell lung cancer. The Lung Cancer Study Group.
复制标题
非小细胞肺癌中视网膜母细胞瘤易感基因的失活。
作者：
Reissmann Pt;H. Koga;Rei Takahashi;Robert A. Figlin;Holmes Ec;Steven T. Piantadosi;Carlos Cordon;D. J. Slamon
阻止视网膜母细胞瘤易感基因（RB）正常表达的突变与多种人类恶性肿瘤的发病机制有关。这种肿瘤抑制基因的突变失活似乎会引发视网膜母细胞瘤的发展，也可能导致骨肉瘤、软组织肉瘤、小细胞肺癌和其他恶性肿瘤的发病机制。我们与肺癌研究组合作，研究了 219 例原发性非小细胞肺癌 (NSCLC) 队列中 RB 基因的结构和表达。通过 Southern blot 和 13 号染色体限制性片段长度多态性分析在 DNA 水平上研究了 RB 基因结构。通过转录本的 Northern 分析和蛋白质 (p105RB) 的免疫组织化学分析来评估 RB 基因的表达。 RB 蛋白的免疫组织化学被证明是检测 Rb 基因失活的最灵敏的方法。在所研究的 53/163 (32%) 个可评估病例中检测到 RB 蛋白染色缺失或异常，而 Northern 分析显示 22/219 例 RB 转录物改变或缺失。 Southern 分析仅发现两例该基因发生结构改变，但 13 号染色体杂合性缺失在无法表达该蛋白质的肿瘤中很常见。对所研究的肿瘤患者的临床结果的分析没有显示 RB 失活与复发或死亡时间之间存在任何相关性。这项研究的数据表明，RB 基因在大量 NSCLC 中失活。这些突变在 NSCLC 发展中可能发挥的作用仍有待确定。
Mutations that prevent the normal expression of the retinoblastoma susceptibility gene (RB) have been linked to the pathogenesis of several human malignancies. Mutational inactivation of this tumor-suppressor gene appears to initiate the development of retinoblastoma, and may also contribute to the pathogenesis of osteosarcomas, soft-tissue sarcomas, small-cell lung cancer and other malignancies. In cooperation with the Lung Cancer Study Group, we studied the structure and expression of the RB gene in a cohort of 219 primary non-small-cell lung cancers (NSCLCs). RB gene structure was studied at the DNA level by Southern blot and chromosome 13 restriction fragment length polymorphism analyses. Expression of the RB gene was evaluated by Northern analysis of the transcript and immunohistochemical analysis of the protein (p105RB). Immunohistochemistry of the RB protein proved to be the most sensitive method for the detection of Rb gene inactivation. Absent or abnormal RB protein staining was detected in 53/163 (32%) evaluable cases studied, while Northern analysis showed 22/219 cases to have an altered or absent RB transcript. Southern analysis revealed only two cases of structural alteration of the gene, but loss of heterozygosity from chromosome 13 was common in tumors that failed to express the protein. Analysis of the clinical outcomes of the patients whose tumors were studied did not show any correlation of RB inactivation with time to relapse or death. The data from this study indicate that the RB gene is inactivated in a significant number of NSCLCs. The role that these mutations may play in the development of NSCLC remains to be defined.