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

Wan-Teck Lim¹  Yi Fang Lee²  Huay Mei Poh³  Joyce A. Tai³  Wen Huan Ling³  Ler Yee Phua³  Yu Xuan Haw³  Say Li Kong³  Xingliang Liu³  Axel M. Hillmer⁴  Swee Jin Tan⁵  Tony Kiat Hon Lim⁶  Yong Wei Chua⁶  Chwee Teck Lim⁷  Trifanny Yeo⁷  Daniel Shao-Weng Tan⁸  Kiley Wei Jen Loh⁸  Quan Sing Ng⁸  Mei Kim Ang⁸  Chee Keong Toh⁸  Yoon Sim Yap⁹  Raymond Chee Hui Ng⁹  Tira J. Tan⁹ 

[1] 0IMCB-NCCS-MP Singapore OncoGenome Laboratory, Institute of Molecular and Cell Biology, Singapore, Singapore;Biolidics Ltd, Singapore, Singapore;Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore, Singapore;Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany;Clearbridge mFluidics Pte Ltd, Singapore, Singapore;Department of Anatomical Pathology, Singapore General Hospital, Singapore, Singapore;Department of Biomedical Engineering, National University of Singapore, Singapore, Singapore;Division of Medical Oncology, National Cancer Center, Singapore, Singapore;Duke-NUS Medical School, Singapore, Singapore;Institute of Pathology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany;

关键词: circulating tumor cells;    cell-free tumor DNA;    amplicon-sequencing;    metastatic signatures;    genomic heterogeneity;    evolving alterations;   

DOI  :  10.3389/fonc.2021.698551

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown