Rothé Françoise, Venet David, Peeters Dieter, Rouas Ghizlane, Rediti Mattia, Smeets Dominiek, Dupont Floriane, Campbell Peter, Lambrechts Diether, Dirix Luc, Sotiriou Christos, Ignatiadis Michail
Breast Cancer Translational Research Laboratory J.-C. Heuson, Université Libre de Bruxelles, Institut Jules Bordet, Brussels, Belgium.
Histopathology, Imaging and Quantification Unit, CellCarta, Antwerp, Belgium.
NPJ Breast Cancer. 2022 Jul 5;8(1):79. doi: 10.1038/s41523-022-00445-7.
Single cell technologies allow the interrogation of tumor heterogeneity, providing insights into tumor evolution and treatment resistance. To better understand whether circulating tumor cells (CTCs) could complement metastatic biopsies for tumor genomic profiling, we characterized 11 single CTCs and 10 pooled CTC samples at the mutational and copy number aberration (CNA) levels, and compared these results with matched synchronous tumor biopsies from 3 metastatic breast cancer patients with triple-negative (TNBC), HER2-positive and estrogen receptor-positive (ER+) tumors. Similar CNA profiles and the same patient-specific driver mutations were found in bulk tissue and CTCs for the HER2-positive and TNBC tumors, whereas different CNA profiles and driver mutations were identified for the ER+ tumor, which presented two distinct clones in CTCs defined by mutations in ESR1 Y537N and TP53, respectively. Furthermore, de novo mutational signatures derived from CTCs described patient-specific biological processes. These data suggest that tumor tissue and CTCs provide complementary clinically relevant information to map tumor heterogeneity and tumor evolution.
单细胞技术能够对肿瘤异质性进行研究，从而深入了解肿瘤的进化和治疗抗性。为了更好地理解循环肿瘤细胞（CTC）是否可以补充转移性活检用于肿瘤基因组分析，我们在突变和拷贝数变异（CNA）水平上对11个单个CTC和10个混合CTC样本进行了表征，并将这些结果与来自3例三阴性（TNBC）、HER2阳性和雌激素受体阳性（ER+）肿瘤的转移性乳腺癌患者的匹配同步肿瘤活检结果进行了比较。在HER2阳性和TNBC肿瘤的大块组织和CTC中发现了相似的CNA谱和相同的患者特异性驱动突变，而ER+肿瘤则鉴定出不同的CNA谱和驱动突变，该肿瘤在CTC中呈现出两个分别由ESR1 Y537N和TP53突变定义的不同克隆。此外，源自CTC的新生突变特征描述了患者特异性的生物学过程。这些数据表明，肿瘤组织和CTC提供了互补的临床相关信息，以描绘肿瘤异质性和肿瘤进化。
