Lung cancer (LC) is the first cause of cancer-related deaths worldwide. Elucidating the pathogenesis of LC will give information on key elements of tumor initiation and development while helping to design novel targeted therapies. LC is an heterogeneous disease that has the second highest mutation rate surpassed only by melanoma, since 90% of LC occurs in tobacco smokers. However, only a small percent of smokers develops LC, indicating an inherent genomic instability. Additionally, LC in never smokers suggests other molecular mechanisms not causally linked to tobacco carcinogens. This review presents a current outlook of the connection between LC and genomic instability at the molecular and clinical level summarizing its implications for diagnosis, therapy, and prognosis. The genomic landscape of LC shows widespread alterations such as DNA methylation, point mutations, copy number variation, chromosomal translocations, and aneuploidy. Genome maintenance mechanisms including cell cycle control, DNA repair, and mitotic checkpoints open a window to translational research for finding novel diagnostic biomarkers and targeted therapies in LC.

中文翻译：

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与肺癌基因组不稳定性相关的多个分子靶标。

肺癌（LC）是全球范围内与癌症相关的死亡的首个原因。阐明LC的发病机理，将在帮助设计新颖的靶向疗法的同时，提供有关肿瘤发生和发展的关键要素的信息。LC是异质性疾病，其突变率仅次于黑色素瘤，是第二高的，因为90％的LC发生在吸烟者中。但是，只有一小部分吸烟者会发展为LC，这表明其固有的基因组不稳定性。此外，从不吸烟者的LC提示与烟草致癌物没有因果关系的其他分子机制。这篇综述从分子和临床的角度介绍了LC与基因组不稳定性之间联系的当前前景，总结了其对诊断，治疗和预后的影响。LC的基因组图谱显示了广泛的变化，例如DNA甲基化，点突变，拷贝数变化，染色体易位和非整倍性。基因组维持机制，包括细胞周期控制，DNA修复和有丝分裂检查点，为寻找LC中新的诊断性生物标志物和靶向疗法的转化研究打开了一个窗口。