Recognition of the organ-specific mutations in metastatic breast cancer by circulating tumor cells isolated in vivo.

Abstract

The failure to treat and control the growth of metastases is the main cause of death in breast cancer (BC) patients. Compared to the traditional method of analyzing circulating tumor DNA (ctDNA), capturing intact circulating tumor cells (CTCs) allows us to more accurately characterize mutations and identify suitable targeted therapies. We used CellCollector to collect peripheral CTCs. Thirty metastatic breast cancer (MBC) patients were enrolled, and 17 were analyzed with next-generation sequencing (NGS) methods. Clinical characteristics were analyzed along with the CTCs enumeration and detection rates. Whole-genome amplification (WGA) was used to amplify the CTC genomic DNA of 127 genes. Patients younger than 45 years old, with brain metastasis, with three or more metastatic sites, or with HER2-positive had the highest number of CTCs collected. The CTCs detection rate was also correlated to the number of metastasis sites. Different metastasis sites such as the brain, viscus, bone, and soft tissue contained specific high-frequency gene mutations. AKT3, MYC, and NT5C2 mutations were only found in brain metastases. APC, BCL2L11, ESRP1, FLT3 mutations were only in the visceral metastases. KEAP1, KIT, MET were the specific mutation genes in patients with bone and soft tissue metastases. These findings provide evidence that we can detect gene mutation information for obtaining the biological characteristics by CTCs using CellCollector. Different metastasis sites contain specific high-frequency mutation genes, which provide guidance to the accurate gene therapy.

A real-world comparison of circulating tumor cells in breast cancer from China: Novel device, CTC counts and its overall survival

“…This also favors the application of CC in clinical due to the high detection rates compared with CS. Previous studies have explored that the detection rate of CC technology in breast cancer patients is on average between 41% and 70% [ 21 , 25 , 26 ]. Although the sensitivity of CC count is lower than that of CS count, the correlation between CTC count detected by CC count and clinical prognosis in breast cancer patients is still very clear.…”

Advances in novel strategies for isolation, characterization, and analysis of CTCs and ctDNA

“…203 Another recent study used NGS to demonstrate that various metastatic sites in the CTCs genome have matching mutation genes. 204 He et al and colleagues employed NGS for 6 CTCs and identified 44 mutant cancer-related genes in CTCs, including KIT, SMARCB1, and TP53 genes. 205 Using NGS-based methods has been associated with some limitations, though.…”

Single-Circulating Tumor Cell Whole Genome Amplification to Unravel Cancer Heterogeneity and Actionable Biomarkers

“…Breast cancer (BC) is the most common female cancer and CTC is a predictive marker of poor survival and metastatic relapse [ 58 ]. The detection rate of CTCs correlates with the number of metastatic sites, and BC patients with brain metastasis may have the highest CTC counts [ 59 ].…”