Marino Elena, Mauro Cristian, Belloni Elena, Picozzi Marco, Favalli Valentina, Cassatella Maria Cristina, Zorzino Laura, Giacò Luciano, Pelicci Pier Giuseppe, Barberis Massimo, Sandri Maria Teresa, Bernard Loris
Clinic Unit of Oncogenomics, IEO, European Institute of Oncology, IRCCS, Milan, Italy.
Laboratory of Medical Genetics, Istituto Europeo di Oncologia, IRCCS, Milan, Italy.
Biochem Biophys Rep. 2024 Aug 26;39:101805. doi: 10.1016/j.bbrep.2024.101805. eCollection 2024 Sep.
In metastatic breast cancer (MBC), blood is a source of circulating tumor cells (CTCs). CTCs may serve as a ''real-time liquid biopsy" as they represent metastatic tumor genetics better than primary tumor. is one of the most important oncogenes in treatment-unresponsive breast cancers. The aim of this study was to detect mutations and hereditary cancer variants in CTCs from MBC patients. Forty-seven blood samples were obtained from 20 MBC patients from at least 1/3 consecutive time points. CTCs were quantified using the CellSearch system and isolated from 11/20 patients with ≥5/7.5 ml CTCs (14/47 blood samples) using the DEPArray system. DNA was extracted and amplified to perform Sanger sequencing on gene. Sequencing revealed a pathogenic mutation in 2/11 (18 %) cases. Subsequently, we evaluated a 26-target hereditary gene panel by Next Generation Sequencing and identified a concomitant pathogenic mutation in the gene in a patient with a mutation. No pathogenic germline variants were found. Our data support the conclusion that CTCs analysis may be used to identify mutations in patients to identify those more likely to metastasize.
在转移性乳腺癌（MBC）中，血液是循环肿瘤细胞（CTC）的来源。CTC可作为一种“实时液体活检”，因为它们比原发性肿瘤更能代表转移性肿瘤遗传学。 是治疗无反应性乳腺癌中最重要的致癌基因之一。本研究的目的是检测MBC患者CTC中的 突变和遗传性癌症变异。从20例MBC患者至少1/3连续时间点采集了47份血样。使用CellSearch系统对CTC进行定量，并使用DEPArray系统从11/20例每7.5毫升血液中CTC≥5个的患者（14/47份血样）中分离出CTC。提取DNA并进行扩增，以对 基因进行桑格测序。测序显示2/11（18%）的病例存在致病性 突变。随后，我们通过下一代测序评估了一个包含26个靶点的遗传性基因panel，并在一名存在 突变的患者中鉴定出 基因同时存在致病性突变。未发现致病性种系变异。我们的数据支持这样的结论，即CTC分析可用于识别患者中的突变，以确定那些更有可能发生转移的患者。
