Soca-Chafre Giovanny, Montiel-Dávalos Angelica, Rosa-Velázquez Inti Alberto De La, Caro-Sánchez Claudia Haydeé Saraí, Peña-Nieves Adriana, Arrieta Oscar
Personalized Medicine Laboratory, Instituto Nacional de Cancerología (INCAN), Mexico.
Basic Research Division, Instituto Nacional de Cancerología (INCAN), Mexico.
Int J Genomics. 2019 Jul 1;2019:9584504. doi: 10.1155/2019/9584504. eCollection 2019.
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.
肺癌（LC）是全球癌症相关死亡的首要原因。阐明肺癌的发病机制将为肿瘤起始和发展的关键要素提供信息，同时有助于设计新型靶向治疗方法。肺癌是一种异质性疾病，其突变率仅次于黑色素瘤，位居第二，因为90%的肺癌发生在吸烟者中。然而，只有一小部分吸烟者会患肺癌，这表明存在内在的基因组不稳定性。此外，从不吸烟者患肺癌表明存在其他与烟草致癌物无因果关系的分子机制。本综述从分子和临床层面介绍了肺癌与基因组不稳定性之间联系的当前观点，总结了其对诊断、治疗和预后的影响。肺癌的基因组格局显示出广泛的改变，如DNA甲基化、点突变、拷贝数变异、染色体易位和非整倍体。包括细胞周期控制、DNA修复和有丝分裂检查点在内的基因组维持机制为肺癌的转化研究打开了一扇窗，有助于寻找新型诊断生物标志物和靶向治疗方法。
