Erramuzpe Asier, Cortés Jesús M, López José I
Quantitative Biomedicine Unit, Biocruces Research Institute, 48903, Barakaldo, Spain.
Ikerbasque: The Basque Foundation for Science, 48013, Bilbao, Spain.
Virchows Arch. 2018 Feb;472(2):187-194. doi: 10.1007/s00428-017-2223-y. Epub 2017 Aug 25.
Intratumor heterogeneity (ITH) is an inherent process of tumor development that has received much attention in previous years, as it has become a major obstacle for the success of targeted therapies. ITH is also temporally unpredictable across tumor evolution, which makes its precise characterization even more problematic since detection success depends on the precise temporal snapshot at which ITH is analyzed. New and more efficient strategies for tumor sampling are needed to overcome these difficulties which currently rely entirely on the pathologist's interpretation. Recently, we showed that a new strategy, the multisite tumor sampling, works better than the routine sampling protocol for the ITH detection when the tumor time evolution was not taken into consideration. Here, we extend this work and compare the ITH detections of multisite tumor sampling and routine sampling protocols across tumor time evolution, and in particular, we provide in silico analyses of both strategies at early and late temporal stages for four different models of tumor evolution (linear, branched, neutral, and punctuated). Our results indicate that multisite tumor sampling outperforms routine protocols in detecting ITH at all different temporal stages of tumor evolution. We conclude that multisite tumor sampling is more advantageous than routine protocols in detecting intratumor heterogeneity.
肿瘤内异质性（ITH）是肿瘤发展的一个固有过程，在过去几年中受到了广泛关注，因为它已成为靶向治疗成功的主要障碍。ITH在肿瘤演变过程中在时间上也是不可预测的，这使得其精确表征更加困难，因为检测成功取决于分析ITH时的精确时间点。需要新的、更有效的肿瘤采样策略来克服目前完全依赖病理学家解释的这些困难。最近，我们表明，当不考虑肿瘤时间演变时，一种新的策略——多部位肿瘤采样，在ITH检测方面比常规采样方案效果更好。在这里，我们扩展了这项工作，比较了多部位肿瘤采样和常规采样方案在肿瘤时间演变过程中的ITH检测情况，特别是，我们针对四种不同的肿瘤演变模型（线性、分支、中性和间断性）在早期和晚期时间阶段对这两种策略进行了计算机模拟分析。我们的结果表明，在肿瘤演变的所有不同时间阶段，多部位肿瘤采样在检测ITH方面优于常规方案。我们得出结论，在检测肿瘤内异质性方面，多部位肿瘤采样比常规方案更具优势。
