Univ Rennes, Inserm, EHESP, Irset - UMR_S1085, F-35000, Rennes 1 University, Rennes, Bretagne, France.
Department of Pathology, University Hospital, Rennes, Bretagne, France.
J Clin Pathol. 2022 Jun;75(6):426-430. doi: 10.1136/jclinpath-2020-207326. Epub 2021 Mar 25.
The dynamics of metastatic evolution in clear cell renal cell carcinoma (ccRCC) are complex. We report a case study where tumour heterogeneity resulting from clonal evolution is a frequent feature and could play a role in metastatic dissemination.We used an integrative multiomics strategy combining genomic and transcriptomic data to classify fourteen specimens from spatially different areas of a kidney tumour and three non-primary sites including a vein thrombus and two adrenal metastases.All sites were heterogeneous and polyclonal, each tumour site containing two different aggressive subclonal populations, with differentially expressed genes implicated in distinct biological functions. These are rare primary metastatic samples prior to any medical treatment, where we showed a multiple metastatic seeding of two subclonal populations.Multiple interdependent lineages could be the source of metastatic heterogeneity in ccRCC. By sampling metastases, patients with resistance to therapies could benefit a combination of targeted therapies based on more than one aggressive clone.
透明细胞肾细胞癌 (ccRCC) 转移进化的动力学十分复杂。我们报告了一个病例研究，其中克隆进化导致的肿瘤异质性是一个常见特征，并可能在转移扩散中发挥作用。我们使用了一种整合的多组学策略，结合基因组和转录组数据，对来自肾脏肿瘤不同空间区域的 14 个标本和三个非原发性部位（包括静脉血栓和两个肾上腺转移）进行分类。所有部位均具有异质性和多克隆性，每个肿瘤部位包含两个不同的侵袭性亚克隆群体，差异表达的基因涉及不同的生物学功能。这些是未经任何治疗的罕见原发性转移性样本，我们展示了两个亚克隆群体的多个转移性播种。多个相互依赖的谱系可能是 ccRCC 转移异质性的来源。通过对转移进行采样，对治疗有耐药性的患者可以从基于一个以上侵袭性克隆的靶向治疗组合中获益。
