基因组不稳定性在肿瘤发生中至关重要，肿瘤突变负荷（TMB）是指示治疗效果的生物标志物，特别是在免疫治疗中。然而，TMB 并不总是可靠的预测因子，并且表现出异质性。非 B DNA 容易发生突变，在癌症发展中发挥着重要作用，这表明它们与突变相结合可增强癌症标记物的潜在价值。我们评估了突变和非 B DNA 作为生物标记物的相互作用。我们的方法通过生存和药物敏感性评估来量化肿瘤突变及其与非 B DNA 的共定位，以实现临床相关性。我们引入了两种新的标记物，“nbTMB”（非 B 信息肿瘤突变负荷）和“mlTNB”（突变局部肿瘤非 B 负担）。在案例研究中：（1）nbTMB 可以了解接受免疫治疗的 TMB 高患者的生存异质性，而 TMB 无法进一步区分； (2) nbTMB 揭示卵巢癌细胞系中顺铂敏感性的改变，而 TMB 无法区分； (3) mlTNB 揭示了早期胰腺癌进展者的生存异质性，其中其他基因组不稳定标记物无法区分这些进展者。这些新标记物提供了一种细致入微的方法，以增强我们对癌症治疗反应和结果的理解，强调需要对非 B 和 B-DNA 特征之间相互作用的全面探索。© 2024。作者。

Genomic instability is crucial in tumorigenesis, with Tumour Mutation Burden (TMB) being a biomarker to indicate therapeutic effectiveness, particularly in immunotherapy. However, TMB is not always a reliable predictor and displays heterogeneity. Non-B DNA, susceptible to mutations, play a significant role in cancer development, indicating their potential merit when combined with mutation for enhanced markers in cancer.We assessed mutations and non-B DNA interplay as biomarkers. Our methodology quantifies tumour mutations and their co-localization with non-B DNA, using survival and drug sensitivity assessments for clinical relevance.We introduce two novel markers, 'nbTMB' (non-B-informed tumour mutation burden) and 'mlTNB' (mutation-localised tumour non-B burden). In case studies: (1) nbTMB informs on survival heterogeneity among TMB-high patients undergoing immunotherapy whereas TMB is unable to further differentiate; (2) nbTMB informs on altered cisplatin sensitivity among ovarian cancer cell lines whereas TMB is unable to differentiate; and (3) mlTNB informs on survival heterogeneity among early-stage pancreatic cancer progressors in whom other markers of genomic instability fail to differentiate.These novel markers offer a nuanced approach to enhance our understanding of treatment responses and outcomes in cancer, underscoring the need for a comprehensive exploration of the interplay between non-B and B-DNA features.© 2024. The Author(s).