Molecular and Genetic Pathogenesis of Lung Cancer: Differences Between Small-Cell and Non-Small-Cell Carcinomas
Molecular and Genetic Pathogenesis of Lung Cancer: Differences Between Small-Cell and Non-Small-Cell Carcinomas
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肺癌的分子和遗传发病机制：小细胞癌和非小细胞癌之间的差异
DOI：
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
Hanako Sato
中科院分区：
文献类型：
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作者：
H. Kitamura;T. Yazawa;K. Okudela;H. Shimoyamada;Hanako Sato
肺癌分为小细胞癌（SCLC）和非小细胞癌（NSCLC）。SCLC和NSCLC之间以及NSCLC亚型之间的分子和遗传学改变概况存在显著差异。TP 53在近50%的NSCLC中失活，而其功能失活突变在SCLC中非常普遍（70-100%）。Rb基因改变和蛋白质丢失在几乎所有的SCLC中发现，但很少在NSCLC中发现。相反，由于Rb途径上游调节因子的功能障碍，Rb功能被废除。TP 53的改变在腺癌中发生较晚，而在鳞状细胞癌发生较早。近年来的研究表明表皮生长因子受体（EGFR）基因的激活突变在腺癌的发生发展中起重要作用。最近在近一半的鳞状细胞癌病例中发现了PIK 3催化α基因的激活。吸烟与Tp 53、K-ras和PIK 3催化α的改变密切相关，但与EGFR基因突变弱相关。总之，Rb和Tp 53基因的沉默改变最有可能是SCLC发展中的重要和早期事件，而EGFR信号通路的改变在NSCLC癌变中起着重要作用。各种类型肺癌的生物学行为和表型可归因于这些分子和遗传改变，但也反映了其前体细胞能力的差异。需要鉴定气道干细胞并阐明其维持和活化的分子机制。
Lung cancer is classified into small-cell carcinoma (SCLC) and non-small-cell carcinoma (NSCLC). The pro- file of molecular and genetic alterations considerably differs between SCLC and NSCLC, as well as among the subtypes of NSCLC. Tp53 is inactivated in nearly 50% of NSCLC, while its mutations with functional inactivation are greatly prevalent in SCLC (70-100%). Rb gene alterations and protein loss are found in virtually all SCLC, but rarely in NSCLC. Instead, the Rb function is abrogated due to dysfunction of the upstream regulators of the Rb pathway. Tp53 alterations are later events in adenocarcinoma, while they occur early in squamous cell carcinoma carcinogenesis. Recent studies demonstrated activating mutations of the epidermal growth factor receptor (EGFR) gene play a significantly important role in adenocarcinoma carcinogenesis. Activation of PIK3 catalytic alpha gene was recently found in nearly half of squamous cell carcinoma cases. Smoking is associated strongly with alterations of Tp53, K-ras, and PIK3 catalytic alpha, but weakly with EGFR gene mutations. Taken together silencing alterations of both the Rb and Tp53 genes are most likely to be important and early events in the development of SCLC, whereas alterations of the EGFR signaling pathway play significant and important roles in NSCLC carcinogenesis. The biological behavior and phenotype of the respective types of lung cancer would be attributable to these molecular and genetic alterations, but also reflect the difference in the ability of their precursor cells. Identifying the airway stem cell(s) and elucidating the molecular mechanism of its mainte- nance and activation are required.
影响因子：
7.5
作者：
Iaquinta, Phillip J.;Lees, Jacqueline A.
通讯作者：
Lees, Jacqueline A.
影响因子：
50.3
作者：
Yun, Cai-Hong;Boggon, Titus J.;Eck, Michael J.
通讯作者：
Eck, Michael J.
影响因子：
50.3
作者：
Meuwissen, R;Linn, SC;Berns, A
通讯作者：
Berns, A