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Chromosomal instability of circulating tumor DNA reflect therapeutic responses in advanced gastric cancer

Gastric cancer is characterized by chromosomal instability. In this study, we investigated chromosomal instability quantified by copy number instability (CNI) score of circulating tumor DNA (ctDNA) during the drug treatment in advanced gastric cancer (AGC). A total of 55 pretherapeutic plasmas from...

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Autores principales: Chen, Zuhua, Zhang, Cheng, Zhang, Mengqi, Li, Beifang, Niu, Yunyun, Chen, Limeng, Yang, Jing, Lu, Sijia, Gao, Jing, Shen, Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754425/
https://www.ncbi.nlm.nih.gov/pubmed/31541076
http://dx.doi.org/10.1038/s41419-019-1907-4
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author Chen, Zuhua
Zhang, Cheng
Zhang, Mengqi
Li, Beifang
Niu, Yunyun
Chen, Limeng
Yang, Jing
Lu, Sijia
Gao, Jing
Shen, Lin
author_facet Chen, Zuhua
Zhang, Cheng
Zhang, Mengqi
Li, Beifang
Niu, Yunyun
Chen, Limeng
Yang, Jing
Lu, Sijia
Gao, Jing
Shen, Lin
author_sort Chen, Zuhua
collection PubMed
description Gastric cancer is characterized by chromosomal instability. In this study, we investigated chromosomal instability quantified by copy number instability (CNI) score of circulating tumor DNA (ctDNA) during the drug treatment in advanced gastric cancer (AGC). A total of 55 pretherapeutic plasmas from 55 AGC patients and 75 plasmas during drug treatment of 26 AGC patients were collected. Plasma ctDNA was extracted and assessed by whole-genome sequencing (WGS) for somatic copy number alteration (SCNA), and according to which we calculated the CNI scores. We next assessed the correlations between chromosomal instability and therapeutic response. The cutoff value of chromosomal instability was defined as the mean + SD of the CNI scores (56.60) in cfDNA of plasmas from 100 healthy people. For 55 enrolled cases, chromosomal instability was observed in 27 (49%) prior to drug treatment, whose response rate (59%, 16/27) was higher than in 28 patients with stable chromosomes (32%, 9/28, P = 0.043). We also observed that CNI scores fluctuated during treatment in 26 patients. Specifically, the CNI scores in 93% (14/15) of patients sensitive to drug treatment reduced to the level of chromosomal stability and the CNI scores in 52% (13/25) of patients resistant to treatment elevated again. For ctDNA with developed resistance, the SCNA patterns were identical to those before treatment, whereas the CNI scores were lower than the pretherapeutic scores. We found that chromosomal instability based on ctDNA could predict and monitor therapeutic response in gastric cancer, although validation in a larger cohort will be necessary.
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spelling pubmed-67544252019-09-23 Chromosomal instability of circulating tumor DNA reflect therapeutic responses in advanced gastric cancer Chen, Zuhua Zhang, Cheng Zhang, Mengqi Li, Beifang Niu, Yunyun Chen, Limeng Yang, Jing Lu, Sijia Gao, Jing Shen, Lin Cell Death Dis Article Gastric cancer is characterized by chromosomal instability. In this study, we investigated chromosomal instability quantified by copy number instability (CNI) score of circulating tumor DNA (ctDNA) during the drug treatment in advanced gastric cancer (AGC). A total of 55 pretherapeutic plasmas from 55 AGC patients and 75 plasmas during drug treatment of 26 AGC patients were collected. Plasma ctDNA was extracted and assessed by whole-genome sequencing (WGS) for somatic copy number alteration (SCNA), and according to which we calculated the CNI scores. We next assessed the correlations between chromosomal instability and therapeutic response. The cutoff value of chromosomal instability was defined as the mean + SD of the CNI scores (56.60) in cfDNA of plasmas from 100 healthy people. For 55 enrolled cases, chromosomal instability was observed in 27 (49%) prior to drug treatment, whose response rate (59%, 16/27) was higher than in 28 patients with stable chromosomes (32%, 9/28, P = 0.043). We also observed that CNI scores fluctuated during treatment in 26 patients. Specifically, the CNI scores in 93% (14/15) of patients sensitive to drug treatment reduced to the level of chromosomal stability and the CNI scores in 52% (13/25) of patients resistant to treatment elevated again. For ctDNA with developed resistance, the SCNA patterns were identical to those before treatment, whereas the CNI scores were lower than the pretherapeutic scores. We found that chromosomal instability based on ctDNA could predict and monitor therapeutic response in gastric cancer, although validation in a larger cohort will be necessary. Nature Publishing Group UK 2019-09-20 /pmc/articles/PMC6754425/ /pubmed/31541076 http://dx.doi.org/10.1038/s41419-019-1907-4 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Chen, Zuhua
Zhang, Cheng
Zhang, Mengqi
Li, Beifang
Niu, Yunyun
Chen, Limeng
Yang, Jing
Lu, Sijia
Gao, Jing
Shen, Lin
Chromosomal instability of circulating tumor DNA reflect therapeutic responses in advanced gastric cancer
title Chromosomal instability of circulating tumor DNA reflect therapeutic responses in advanced gastric cancer
title_full Chromosomal instability of circulating tumor DNA reflect therapeutic responses in advanced gastric cancer
title_fullStr Chromosomal instability of circulating tumor DNA reflect therapeutic responses in advanced gastric cancer
title_full_unstemmed Chromosomal instability of circulating tumor DNA reflect therapeutic responses in advanced gastric cancer
title_short Chromosomal instability of circulating tumor DNA reflect therapeutic responses in advanced gastric cancer
title_sort chromosomal instability of circulating tumor dna reflect therapeutic responses in advanced gastric cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754425/
https://www.ncbi.nlm.nih.gov/pubmed/31541076
http://dx.doi.org/10.1038/s41419-019-1907-4
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