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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
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 an...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322849/ https://www.ncbi.nlm.nih.gov/pubmed/34336686 http://dx.doi.org/10.3389/fonc.2021.698551 |
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author | 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 |
author_facet | 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 |
author_sort | Kong, Say Li |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8322849 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83228492021-07-31 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 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 Front Oncol Oncology 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. Frontiers Media S.A. 2021-07-16 /pmc/articles/PMC8322849/ /pubmed/34336686 http://dx.doi.org/10.3389/fonc.2021.698551 Text en Copyright © 2021 Kong, Liu, Tan, Tai, Phua, Poh, Yeo, Chua, Haw, Ling, Ng, Tan, Loh, Tan, Ng, Ang, Toh, Lee, Lim, Lim, Hillmer, Yap and Lim https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology 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 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 |
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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322849/ https://www.ncbi.nlm.nih.gov/pubmed/34336686 http://dx.doi.org/10.3389/fonc.2021.698551 |
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