A multitude of exogenous and endogenous processes have the potential to result in DNA damage. While the repair mechanisms are typically capable of correcting this damage, errors in the repair process can result in mutations. The findings of research conducted in 2012 indicate that mutations do not occur randomly but rather follow specific patterns that can be attributed to known or inferred mutational processes. The process of mutational signature analysis allows for the inference of the predominant mutational process for a given cancer sample, with significant potential for clinical applications. A deeper comprehension of these mutational signatures in CRC could facilitate enhanced prevention strategies, facilitate the comprehension of genotoxic drug activity, predict responses to personalized treatments, and, in the future, inform the development of targeted therapies in the context of precision oncology. The efforts of numerous researchers have led to the identification of several mutational signatures, which can be categorized into different mutational signature references. In CRC, distinct mutational signatures are identified as correlating with mismatch repair deficiency, polymerase mutations, and chemotherapy treatment. In this context, a mutational signature analysis offers considerable potential for enhancing minimal residual disease (MRD) tests in stage II (high-risk) and stage III CRC post-surgery, stratifying CRC based on the impacts of genetic and epigenetic alterations for precision oncology, identifying potential therapeutic vulnerabilities, and evaluating drug efficacy and guiding therapy, as illustrated in a proof-of-concept clinical trial.
多种外源性和内源性过程均可能导致DNA损伤。尽管修复机制通常能够纠正这些损伤，但修复过程中的错误仍可能引发突变。2012年的研究表明，突变并非随机发生，而是遵循特定模式，这些模式可归因于已知或推测的突变过程。突变特征分析能够推断特定癌症样本中的主要突变过程，具有显著的临床应用潜力。深入理解结直肠癌中的这些突变特征，有助于优化预防策略、理解基因毒性药物活性、预测个体化治疗反应，并为未来精准肿瘤学背景下靶向治疗的开发提供依据。众多研究者的努力已识别出多种突变特征，这些特征可归类于不同的突变特征参考集。在结直肠癌中，特定的突变特征被确认与错配修复缺陷、聚合酶突变及化疗治疗相关。在此背景下，突变特征分析展现出巨大潜力：可优化II期（高风险）和III期结直肠癌术后微小残留病灶检测，基于遗传和表观遗传改变的影响对结直肠癌进行分层以实现精准肿瘤治疗，识别潜在治疗薄弱点，并通过概念验证性临床试验评估药物疗效及指导治疗。
肿瘤(癌症)患者之家