| Autor: |
Say Li Kong, Xingliang Liu, Swee Jin Tan, Joyce A. Tai, Ler Yee Phua, Huay Mei Poh, Trifanny Yeo, Yong Wei Chua, Yu Xuan Haw, Wen Huan Ling, Raymond Chee Hui Ng, Tira J. Tan, Kiley Wei Jen Loh, Daniel Shao-Weng Tan, Quan Sing Ng, Mei Kim Ang, Chee Keong Toh, Yi Fang Lee, Chwee Teck Lim, Tony Kiat Hon Lim, Axel M. Hillmer, Yoon Sim Yap, Wan-Teck Lim |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Frontiers in Oncology, Vol 11 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2234-943X |
| DOI: |
10.3389/fonc.2021.698551 |
| Popis: |
IntroductionCirculating 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.MethodsConcurrent 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.ResultsHigher 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.ConclusionsA 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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