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LiquidCNA: Tracking subclonal evolution from longitudinal liquid biopsies using somatic copy number alterations
Cell-free DNA (cfDNA) measured via liquid biopsies provides a way for minimally invasive monitoring of tumor evolutionary dynamics during therapy. Here we present liquidCNA, a method to track subclonal evolution from longitudinally collected cfDNA samples sequenced through cost-effective low-pass wh...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350516/ https://www.ncbi.nlm.nih.gov/pubmed/34401670 http://dx.doi.org/10.1016/j.isci.2021.102889 |
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author | Lakatos, Eszter Hockings, Helen Mossner, Maximilian Huang, Weini Lockley, Michelle Graham, Trevor A. |
author_facet | Lakatos, Eszter Hockings, Helen Mossner, Maximilian Huang, Weini Lockley, Michelle Graham, Trevor A. |
author_sort | Lakatos, Eszter |
collection | PubMed |
description | Cell-free DNA (cfDNA) measured via liquid biopsies provides a way for minimally invasive monitoring of tumor evolutionary dynamics during therapy. Here we present liquidCNA, a method to track subclonal evolution from longitudinally collected cfDNA samples sequenced through cost-effective low-pass whole-genome sequencing. LiquidCNA utilizes somatic copy number alteration (SCNA) to simultaneously genotype and quantify the size of the dominant subclone without requiring B-allele frequency information, matched-normal samples, or prior knowledge on the genetic identity of the emerging clone. We demonstrate the accuracy of liquidCNA in synthetically generated sample sets and in vitro mixtures of cancer cell lines. In vivo application in patients with metastatic lung cancer reveals the progressive emergence of a novel tumor subpopulation. LiquidCNA is straightforward to use, is computationally inexpensive, and enables continuous monitoring of subclonal evolution to understand and control-therapy-induced resistance. |
format | Online Article Text |
id | pubmed-8350516 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-83505162021-08-15 LiquidCNA: Tracking subclonal evolution from longitudinal liquid biopsies using somatic copy number alterations Lakatos, Eszter Hockings, Helen Mossner, Maximilian Huang, Weini Lockley, Michelle Graham, Trevor A. iScience Article Cell-free DNA (cfDNA) measured via liquid biopsies provides a way for minimally invasive monitoring of tumor evolutionary dynamics during therapy. Here we present liquidCNA, a method to track subclonal evolution from longitudinally collected cfDNA samples sequenced through cost-effective low-pass whole-genome sequencing. LiquidCNA utilizes somatic copy number alteration (SCNA) to simultaneously genotype and quantify the size of the dominant subclone without requiring B-allele frequency information, matched-normal samples, or prior knowledge on the genetic identity of the emerging clone. We demonstrate the accuracy of liquidCNA in synthetically generated sample sets and in vitro mixtures of cancer cell lines. In vivo application in patients with metastatic lung cancer reveals the progressive emergence of a novel tumor subpopulation. LiquidCNA is straightforward to use, is computationally inexpensive, and enables continuous monitoring of subclonal evolution to understand and control-therapy-induced resistance. Elsevier 2021-07-21 /pmc/articles/PMC8350516/ /pubmed/34401670 http://dx.doi.org/10.1016/j.isci.2021.102889 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lakatos, Eszter Hockings, Helen Mossner, Maximilian Huang, Weini Lockley, Michelle Graham, Trevor A. LiquidCNA: Tracking subclonal evolution from longitudinal liquid biopsies using somatic copy number alterations |
title | LiquidCNA: Tracking subclonal evolution from longitudinal liquid biopsies using somatic copy number alterations |
title_full | LiquidCNA: Tracking subclonal evolution from longitudinal liquid biopsies using somatic copy number alterations |
title_fullStr | LiquidCNA: Tracking subclonal evolution from longitudinal liquid biopsies using somatic copy number alterations |
title_full_unstemmed | LiquidCNA: Tracking subclonal evolution from longitudinal liquid biopsies using somatic copy number alterations |
title_short | LiquidCNA: Tracking subclonal evolution from longitudinal liquid biopsies using somatic copy number alterations |
title_sort | liquidcna: tracking subclonal evolution from longitudinal liquid biopsies using somatic copy number alterations |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350516/ https://www.ncbi.nlm.nih.gov/pubmed/34401670 http://dx.doi.org/10.1016/j.isci.2021.102889 |
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