Interrogating breast cancer heterogeneity using single and pooled circulating tumor cell analysis.
Françoise RothéDavid VenetDieter PeetersGhizlane RouasMattia ReditiDominiek SmeetsFloriane DupontPeter CampbellDiether LambrechtsLuc DirixChristos SotiriouMichail IgnatiadisPublished in: NPJ breast cancer (2022)
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.
Keyphrases
- circulating tumor cells
- single cell
- circulating tumor
- estrogen receptor
- copy number
- squamous cell carcinoma
- small cell lung cancer
- healthcare
- rna seq
- stem cells
- genome wide
- metastatic breast cancer
- deep learning
- mesenchymal stem cells
- young adults
- high throughput
- study protocol
- cell free
- double blind
- endoplasmic reticulum