Single-Cell Analysis of Circulating Tumor Cells

Thiele, Jana-Aletta; Pitule, Pavel; Hicks, James; Kühn, Peter

doi:10.1007/978-1-4939-9004-7_17

Cited by 25 publications

(17 citation statements)

References 29 publications

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“…The lysed cell mixture was thawed and underwent whole-genome amplification (WGA) and sequencing library construction as previously reported ( Dago et al 2014 ; Thiele et al 2019 ). Briefly, WGA was done using the WGA4 Genomeplex Single Cell Whole-Genome Amplification Kit (Sigma-Aldrich) followed by purification with the QIAquick PCR Purification Kit (QIAGEN).…”

Section: Methodsmentioning

confidence: 99%

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Treatment response and tumor evolution: lessons from an extended series of multianalyte liquid biopsies in a metastatic breast cancer patient

Welter

McKinley

et al. 2020

Cold Spring Harb Mol Case Stud

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Currently, clinical characterization of metastatic breast cancer is based on tissue samples taken at time of diagnosis. However, tissue biopsies are invasive and tumors are continuously evolving, which indicates the need for minimally invasive longitudinal assessment of the tumor. Blood-based liquid biopsies provide minimal invasive means for serial sampling over the course of treatment and the opportunity to adjust therapies based on molecular markers. Here, we aim to identify cellular changes that occur in breast cancer over the lifespan of an affected patient through single-cell proteomic and genomic analysis of longitudinally sampled solid and liquid biopsies. Three solid and 17 liquid biopsies from peripheral blood of an ER+/HER2− metastatic breast cancer patient collected over 4 years and eight treatment regimens were analyzed for morphology, protein expression, copy-number alterations, and single-nucleotide variations. Analysis of 563 single morphometrically similar circulating tumor cells (CTCs) and 13 cell-free DNA (cfDNA) samples along with biopsies of the primary and metastatic tumor revealed progressive genomic evolution away from the primary tumor profiles, along with changes in ER expression and the appearance of resistance mutations. Both the abundance and the genomic alterations of CTCs and cfDNA were highly correlated and consistent with genomic alterations in the tissue samples. We demonstrate that genomic evolution and acquisition of drug resistance can be detected in real time and at single-cell resolution through liquid biopsy analytes and highlight the utility of liquid biopsies to guide treatment decisions.

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Section: Methodsmentioning

confidence: 99%

“…The lysed cell mixture was thawed and underwent whole genome amplification (WGA) and sequencing library construction as previously reported (Dago et al 2014;Thiele et al 2019).…”

Section: Isolation Of Single Cellsmentioning

confidence: 99%

Treatment response and tumor evolution: lessons from an extended series of multianalyte liquid biopsies in a metastatic breast cancer patient

Welter

McKinley

et al. 2020

Cold Spring Harb Mol Case Stud

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“…To overcome this issue and to possibly link the information on residual disease coming from both bone marrow and extramedullary sites, liquid biopsy approaches are beginning to emerge. Currently under exploration are the detections at high sensitivity levels of circulating tumor DNA (70), circulating plasma cells (71), and M protein peptides (72)(73)(74). The further optimization of the available techniques will be essential for their future success.…”

Section: How To Address Spatial Heterogeneity?mentioning

confidence: 99%

Clinical Applications and Future Directions of Minimal Residual Disease Testing in Multiple Myeloma

et al. 2020

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In the last years, the life expectancy of multiple myeloma (MM) patients has substantially improved thanks to the availability of many new drugs. Our ability to induce deep responses has improved as well, and the treatment goal in patients tolerating treatment moved from the delay of progression to the induction of the deepest possible response. As a result of these advances, a great scientific effort has been made to redefine response monitoring, resulting in the development and validation of high-sensitivity techniques to detect minimal residual disease (MRD). In 2016, the International Myeloma Working Group (IMWG) updated MM response categories defining MRD-negative responses both in the bone marrow (assessed by next-generation flow cytometry or next-generation sequencing) and outside the bone marrow. MRD is an important factor independently predicting prognosis during MM treatment. Moreover, using novel combination therapies, MRD-negative status can be achieved in a fairly high percentage of patients. However, many questions regarding the clinical use of MRD status remain unanswered. MRD monitoring can guide treatment intensity, although well-designed clinical trials are needed to demonstrate this potential. This mini-review will focus on currently available techniques and data on MRD testing and their potential future applications.

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“…Платформа имеет 4 интегрированных компонента: 1) разделение на основе отделения слоя лейкоцитов от эритроцитов и плазмы путем центрифугирования, позволяющего фракционировать клетки крови на основе различий их плавучей плотности, и выделение фракции ядерных клеток, включающей ЦОК, с последующим нанесением образца на предметные стекла микроскопа; 2) автоматическое многопараметрическое флуоресцентное окрашивание; 3) сканирование, анализ и просмотр изображений; 4) механический поиск ЦОК [31]. Высокоразрешающий анализ единичных клеток (the high-definition single-cell analysis, HD-SCA) сочетает выявление всей популяции ЦОК и редких опухоль-ассоциированных клеток и последующий геномный анализ для обнаружения отдельных субпопуляций с учетом молекулярных и морфологических особенностей [32]. Применение этих подходов к ОНПЛ должно улучшить выявление ЦОК при ОНПЛ, которые, согласно природе заболевания, возможно, потеряли свои эпителиальные маркеры.…”

Section: обзорные статьиunclassified

The prospect of using liquid biopsy in diagnosis and treatment strategy in patients with carcinomas of unknown primary

et al. 2021

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Background. The search and use of new molecular prognostic and predictive markers of efficacy detected by liquid biopsy are aimed at understanding the biology of Carcinomas of Unknown Primary (CUP) and improving results of patient treatment. The review is devoted to advances in scientific and clinical research on this issue.Materials and methods. In order to assess the current state of the problem, a search and analysis of relevant data of the scientific databases PubMed, Medline, RISC was carried out.Results. The scientific rationale for the use of liquid biopsy in clinical practice to improve the treatment of cancer patients with CUP is presented. The results of the use of modern approaches to the analysis of fluid biopsy samples in CUP are presented. In particular, the features of using circulating free DNA, circulating tumor DNA, circulating tumor cells in the analysis are considered. The modern possibilities of determining tissue specificity using liquid biopsy in CUP are discussed. The prospects for the development of liquid biopsy for improving diagnostics, determining the prognosis of the disease, and choosing a strategy for treating CUP and the treatment monitoring have been determined.Conclusion. A review of the literature confirms that modern methods of molecular profiling of tumor cells obtained both as a result of liquid biopsy and tissue biopsies will make a significant contribution to the determination of tissue specificity, molecular characteristics of CUP for a personalized approach in order to improve strategies and treatment outcomes for patients with CUP.

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Single-Cell Analysis of Circulating Tumor Cells

Cited by 25 publications

References 29 publications

Treatment response and tumor evolution: lessons from an extended series of multianalyte liquid biopsies in a metastatic breast cancer patient

Treatment response and tumor evolution: lessons from an extended series of multianalyte liquid biopsies in a metastatic breast cancer patient

Clinical Applications and Future Directions of Minimal Residual Disease Testing in Multiple Myeloma

The prospect of using liquid biopsy in diagnosis and treatment strategy in patients with carcinomas of unknown primary

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