Please use this identifier to cite or link to this item: https://doi.org/10.3389/fonc.2021.698551
Title: Complementary Sequential Circulating Tumor Cell (CTC) and Cell-Free Tumor DNA (ctDNA) Profiling Reveals Metastatic Heterogeneity and Genomic Changes in Lung Cancer and Breast Cancer
Authors: Kong, Say Li
Liu, Xingliang
Tan, Swee Jin
Tai, Joyce A
Phua, Ler Yee
Poh, Huay Mei 
Yeo, Trifanny
Chua, Yong Wei
Haw, Yu Xuan
Ling, Wen Huan 
Ng, Raymond Chee Hui 
Tan, Tira J 
Loh, Kiley Wei Jen 
Tan, Daniel Shao-Weng 
Ng, Quan Sing 
Ang, Mei Kim 
Toh, Chee Keong
Lee, Yi Fang
Lim, Chwee Teck 
Lim, Tony Kiat Hon
Hillmer, Axel M
Yap, Yoon Sim 
Lim, Wan-Teck 
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
circulating tumor cells
cell-free tumor DNA
amplicon-sequencing
metastatic signatures
genomic heterogeneity
evolving alterations
lung cancer
breast cancer
MOLECULAR CHARACTERIZATION
EXPRESSION
SURVIVAL
MUTATION
ADENOCARCINOMA
SINGLE
NOTCH1
Issue Date: 16-Jul-2021
Publisher: FRONTIERS MEDIA SA
Citation: Kong, Say Li, Liu, Xingliang, Tan, Swee Jin, Tai, Joyce A, Phua, Ler Yee, Poh, Huay Mei, Yeo, Trifanny, Chua, Yong Wei, Haw, Yu Xuan, Ling, Wen Huan, Ng, Raymond Chee Hui, Tan, Tira J, Loh, Kiley Wei Jen, Tan, Daniel Shao-Weng, Ng, Quan Sing, Ang, Mei Kim, Toh, Chee Keong, Lee, Yi Fang, Lim, Chwee Teck, Lim, Tony Kiat Hon, Hillmer, Axel M, Yap, Yoon Sim, Lim, Wan-Teck (2021-07-16). Complementary Sequential Circulating Tumor Cell (CTC) and Cell-Free Tumor DNA (ctDNA) Profiling Reveals Metastatic Heterogeneity and Genomic Changes in Lung Cancer and Breast Cancer. FRONTIERS IN ONCOLOGY 11. ScholarBank@NUS Repository. https://doi.org/10.3389/fonc.2021.698551
Abstract: Introduction: Circulating tumor cells (CTCs) and cell-free tumor DNA (ctDNA) are tumor components present in circulation. Due to the limited access to both CTC enrichment platforms and ctDNA sequencing in most laboratories, they are rarely analyzed together. Methods: Concurrent isolation of ctDNA and single CTCs were isolated from lung cancer and breast cancer patients using the combination of size-based and CD45-negative selection method via DropCell platform. We performed targeted amplicon sequencing to evaluate the genomic heterogeneity of CTCs and ctDNA in lung cancer and breast cancer patients. Results: Higher degrees of genomic heterogeneity were observed in CTCs as compared to ctDNA. Several shared alterations present in CTCs and ctDNA were undetected in the primary tumor, highlighting the intra-tumoral heterogeneity of tumor components that were shed into systemic circulation. Accordingly, CTCs and ctDNA displayed higher degree of concordance with the metastatic tumor than the primary tumor. The alterations detected in circulation correlated with worse survival outcome for both lung and breast cancer patients emphasizing the impact of the metastatic phenotype. Notably, evolving genetic signatures were detected in the CTCs and ctDNA samples during the course of treatment and disease progression. Conclusions: A standardized sample processing and data analysis workflow for concurrent analysis of CTCs and ctDNA successfully dissected the heterogeneity of metastatic tumor in circulation as well as the progressive genomic changes that may potentially guide the selection of appropriate therapy against evolving tumor clonality.
Source Title: FRONTIERS IN ONCOLOGY
URI: https://scholarbank.nus.edu.sg/handle/10635/218516
ISSN: 2234943X
DOI: 10.3389/fonc.2021.698551
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