Department of Internal Medicine, Yale School of Medicine, New Haven, CT, United States.
Department of Pulmonary Medicine, Brigham and Women's Hospital, Boston, MA, 02115, United States.
Oncologist. 2024 Oct 3;29(10):833-841. doi: 10.1093/oncolo/oyae091.
The genome of a cell is continuously battered by a plethora of exogenous and endogenous processes that can lead to damaged DNA. Repair mechanisms correct this damage most of the time, but failure to do so leaves mutations. Mutations do not occur in random manner, but rather typically follow a more or less specific pattern due to known or imputed mutational processes. Mutational signature analysis is the process by which the predominant mutational process can be inferred for a cancer and can be used in several contexts to study both the genesis of cancer and its response to therapy. Recent pan-cancer genomic efforts such as "The Cancer Genome Atlas" have identified numerous mutational signatures that can be categorized into single base substitutions, doublet base substitutions, or small insertions/deletions. Understanding these mutational signatures as they occur in non-small lung cancer could improve efforts at prevention, predict treatment response to personalized treatments, and guide the development of therapies targeting tumor evolution. For non-small cell lung cancer, several mutational signatures have been identified that correlate with exposures such as tobacco smoking and radon and can also reflect endogenous processes such as aging, APOBEC activity, and loss of mismatch repair. Herein, we provide an overview of the current knowledge of mutational signatures in non-small lung cancer.
细胞的基因组不断受到大量内外源过程的冲击，这些过程可能导致 DNA 损伤。修复机制大多数时候可以纠正这种损伤，但如果修复失败，就会留下突变。突变不是随机发生的，而是由于已知或推断的突变过程，通常遵循或多或少特定的模式。突变特征分析是推断癌症中主要突变过程的过程，可用于多种情况下研究癌症的发生及其对治疗的反应。最近的泛癌症基因组学研究，如“癌症基因组图谱”，已经确定了许多突变特征，这些特征可以分为单碱基替换、双碱基替换或小插入/缺失。了解非小细胞肺癌中发生的这些突变特征，可以改善预防措施，预测针对个性化治疗的治疗反应，并指导针对肿瘤进化的治疗方法的开发。对于非小细胞肺癌，已经确定了一些与吸烟、氡暴露等相关的突变特征，也可以反映衰老、APOBEC 活性和错配修复缺失等内源性过程。本文综述了非小细胞肺癌中突变特征的最新知识。
