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Dissecting Molecular Heterogeneity of Circulating Tumor Cells (CTCs) from Metastatic Breast Cancer Patients through Copy Number Aberration (CNA) and Single Nucleotide Variant (SNV) Single Cell Analysis
| Content Provider | MDPI |
|---|---|
| Author | Rossi, Tania Angeli, Davide Tebaldi, Michela Fici, Pietro Rossi, Elisabetta Rocca, Andrea Palleschi, Michela Maltoni, Roberta Martinelli, Giovanni Fabbri, Francesco Gallerani, Giulia |
| Copyright Year | 2022 |
| Description | Circulating tumor cells’ (CTCs) heterogeneity contributes to counteract their introduction in clinical practice. Through single-cell sequencing we aim at exploring CTC heterogeneity in metastatic breast cancer (MBC) patients. Single CTCs were isolated using DEPArray NxT. After whole genome amplification, libraries were prepared for copy number aberration (CNA) and single nucleotide variant (SNV) analysis and sequenced using Ion GeneStudio S5 and Illumina MiSeq, respectively. CTCs demonstrate distinctive mutational signatures but retain molecular traces of their common origin. CNA profiling identifies frequent aberrations involving critical genes in pathogenesis: gains of 1q (CCND1) and 11q (WNT3A), loss of 22q (CHEK2). The longitudinal single-CTC analysis allows tracking of clonal selection and the emergence of resistance-associated aberrations, such as gain of a region in 12q (CDK4). A group composed of CTCs from different patients sharing common traits emerges. Further analyses identify losses of 15q and enrichment of terms associated with pseudopodium formation as frequent and exclusive events. CTCs from MBC patients are heterogeneous, especially concerning their mutational status. The single-cell analysis allows the identification of aberrations associated with resistance, and is a candidate tool to better address treatment strategy. The translational significance of the group populated by similar CTCs should be elucidated. |
| Starting Page | 3925 |
| e-ISSN | 20726694 |
| DOI | 10.3390/cancers14163925 |
| Journal | Cancers |
| Issue Number | 16 |
| Volume Number | 14 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2022-08-14 |
| Access Restriction | Open |
| Subject Keyword | Cancers Oncology Metastatic Breast Cancer Circulating Tumor Cells Copy Number Aberrations Single Nucleotide Variants Single Cell Sequencing Next Generation Sequencing Liquid Biopsy |
| Content Type | Text |
| Resource Type | Article |
