PMID- 33562741 OWN - NLM STAT- MEDLINE DCOM- 20211102 LR - 20211102 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 10 IP - 2 DP - 2021 Feb 5 TI - Tumor Evolution and Therapeutic Choice Seen through a Prism of Circulating Tumor Cell Genomic Instability. LID - 10.3390/cells10020337 [doi] LID - 337 AB - Circulating tumor cells (CTCs) provide an accessible tool for investigating tumor heterogeneity and cell populations with metastatic potential. Although an in-depth molecular investigation is limited by the extremely low CTC count in circulation, significant progress has been made recently in single-cell analytical processes. Indeed, CTC monitoring through molecular and functional characterization may provide an understanding of genomic instability (GI) molecular mechanisms, which contribute to tumor evolution and emergence of resistant clones. In this review, we discuss the sources and consequences of GI seen through single-cell analysis of CTCs in different types of tumors. We present a detailed overview of chromosomal instability (CIN) in CTCs assessed by fluorescence in situ hybridization (FISH), and we reveal utility of CTC single-cell sequencing in identifying copy number alterations (CNA) oncogenic drivers. We highlight the role of CIN in CTC-driven metastatic progression and acquired resistance, and we comment on the technical obstacles and challenges encountered during single CTC analysis. We focus on the DNA damage response and depict DNA-repair-related dynamic biomarkers reported to date in CTCs and their role in predicting response to genotoxic treatment. In summary, the suggested relationship between genomic aberrations in CTCs and prognosis strongly supports the potential utility of GI monitoring in CTCs in clinical risk assessment and therapeutic choice. FAU - Tayoun, Tala AU - Tayoun T AD - Gustave Roussy, Universite Paris-Saclay, "Circulating Tumor Cells" Translational Platform, CNRS UMS3655-INSERM US23AMMICA, F-94805 Villejuif, France. AD - Gustave Roussy, INSERM, U981 "Molecular Predictors and New Targets in Oncology", F-94805 Villejuif, France. AD - Faculty of Medicine, Universite Paris-Saclay, F-94270 Le Kremlin-Bicetre, France. FAU - Oulhen, Marianne AU - Oulhen M AD - Gustave Roussy, Universite Paris-Saclay, "Circulating Tumor Cells" Translational Platform, CNRS UMS3655-INSERM US23AMMICA, F-94805 Villejuif, France. AD - Gustave Roussy, INSERM, U981 "Molecular Predictors and New Targets in Oncology", F-94805 Villejuif, France. FAU - Aberlenc, Agathe AU - Aberlenc A AD - Gustave Roussy, Universite Paris-Saclay, "Circulating Tumor Cells" Translational Platform, CNRS UMS3655-INSERM US23AMMICA, F-94805 Villejuif, France. AD - Gustave Roussy, INSERM, U981 "Molecular Predictors and New Targets in Oncology", F-94805 Villejuif, France. FAU - Farace, Francoise AU - Farace F AD - Gustave Roussy, Universite Paris-Saclay, "Circulating Tumor Cells" Translational Platform, CNRS UMS3655-INSERM US23AMMICA, F-94805 Villejuif, France. AD - Gustave Roussy, INSERM, U981 "Molecular Predictors and New Targets in Oncology", F-94805 Villejuif, France. FAU - Pawlikowska, Patrycja AU - Pawlikowska P AD - Gustave Roussy, INSERM, U981 "Molecular Predictors and New Targets in Oncology", F-94805 Villejuif, France. LA - eng GR - NA/Ligue Contre le Cancer/ PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20210205 PL - Switzerland TA - Cells JT - Cells JID - 101600052 SB - IM MH - Chromosomal Instability/*genetics MH - DNA Copy Number Variations/*genetics MH - DNA Damage/*genetics MH - DNA Repair/*genetics MH - Genomic Instability/*genetics MH - Genomics/*methods MH - Humans MH - Prognosis PMC - PMC7915006 OTO - NOTNLM OT - DNA-repair OT - chromosomal instability OT - circulating tumor cells OT - genomic instability OT - tumor genetic heterogeneity COIS- The authors declare no conflict of interest. EDAT- 2021/02/11 06:00 MHDA- 2021/11/03 06:00 PMCR- 2021/02/05 CRDT- 2021/02/10 01:02 PHST- 2021/01/13 00:00 [received] PHST- 2021/01/29 00:00 [revised] PHST- 2021/02/02 00:00 [accepted] PHST- 2021/02/10 01:02 [entrez] PHST- 2021/02/11 06:00 [pubmed] PHST- 2021/11/03 06:00 [medline] PHST- 2021/02/05 00:00 [pmc-release] AID - cells10020337 [pii] AID - cells-10-00337 [pii] AID - 10.3390/cells10020337 [doi] PST - epublish SO - Cells. 2021 Feb 5;10(2):337. doi: 10.3390/cells10020337.