Department for BioMedical Research, University of Bern, Bern, Switzerland.
Bern Center for Precision Medicine, University of Bern, Bern, Switzerland.
Prostate. 2022 Aug;82 Suppl 1(Suppl 1):S13-S24. doi: 10.1002/pros.24353.
The landscape of somatic mutations in prostate cancer (PCa) has quickly evolved over the past years.
This evolution was in part due to the improved quality and lower cost of genomic sequencing platforms available to an ever-larger group of clinicians and researchers. The result of these efforts is a better understanding of early and late mutations that are enriched or nearly exclusive to treated PCa. There are, however, some important limitations to the current knowledge. The expanding variety of next-generation sequencing (NGS) assays either capture a wide spectrum of mutations but at low coverage or are focused panels that cover a select number of genes, most often cancer-related, at a deep coverage. Both of these approaches have their advantages, but ultimately miss low-frequency mutations or fail to cover the spectrum of potential mutations. Additionally, some alterations, such as the common ETS gene fusions, require a mixture of DNA and RNA analysis to capture the true frequency. Finally, almost all studies rely on bulk PCa tumor samples, which fail to consider tumor heterogeneity. Given all these caveats, the true picture of the somatic landscape of PCa continues to develop.
In this review, the focus will be on how the landscape of mutations evolves during disease progression considering therapy. It will focus on a select group of early and late mutations and utilize SPOP mutations to illustrate recurrent alterations that may have clinical implications.
近年来，前列腺癌（PCa）体细胞突变的研究领域迅速发展。
这一演变部分归因于基因组测序平台质量的提高和成本的降低，越来越多的临床医生和研究人员能够使用这些平台。这些努力的结果是，人们对早期和晚期突变有了更好的理解，这些突变在接受治疗的 PCa 中更为丰富或几乎是特异性的。然而，目前的知识仍然存在一些重要的局限性。不断扩展的下一代测序（NGS）检测方法要么可以捕获广泛的突变，但覆盖度低，要么是针对少数基因（通常是癌症相关基因）进行深度覆盖的重点面板。这两种方法都有其优势，但最终都会错过低频突变，或者无法覆盖潜在突变的范围。此外，一些改变，如常见的 ETS 基因融合，需要混合 DNA 和 RNA 分析来捕获真实的频率。最后，几乎所有的研究都依赖于前列腺癌肿瘤的混合样本，而无法考虑肿瘤异质性。考虑到所有这些注意事项，PCa 体细胞景观的真实情况仍在不断发展。
在这篇综述中，我们将重点讨论在考虑治疗的情况下，突变景观在疾病进展过程中的演变。它将集中讨论一组早期和晚期的突变，并利用 SPOP 突变来说明可能具有临床意义的反复改变。
