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 and Lim, Wan-Teck ORCID: 0000-0002-4655-0206 (2021). 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. Front. Oncol., 11. LAUSANNE: FRONTIERS MEDIA SA. ISSN 2234-943X

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kong, Say LiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liu, XingliangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tan, Swee JinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tai, Joyce A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Phua, Ler YeeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Poh, Huay MeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yeo, TrifannyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chua, Yong WeiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Haw, Yu XuanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ling, Wen HuanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ng, Raymond Chee HuiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tan, Tira J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loh, Kiley Wei JenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tan, Daniel Shao-WengUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ng, Quan SingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ang, Mei KimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Toh, Chee KeongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lee, Yi FangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lim, Chwee TeckUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lim, Tony Kiat HonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hillmer, Axel M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yap, Yoon SimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lim, Wan-TeckUNSPECIFIEDorcid.org/0000-0002-4655-0206UNSPECIFIED
URN: urn:nbn:de:hbz:38-597244
DOI: 10.3389/fonc.2021.698551
Journal or Publication Title: Front. Oncol.
Volume: 11
Date: 2021
Publisher: FRONTIERS MEDIA SA
Place of Publication: LAUSANNE
ISSN: 2234-943X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MOLECULAR CHARACTERIZATION; EXPRESSION; SURVIVAL; MUTATION; ADENOCARCINOMA; SINGLE; NOTCH1Multiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/59724

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