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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...

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Autores principales: Lakatos, Eszter, Hockings, Helen, Mossner, Maximilian, Huang, Weini, Lockley, Michelle, Graham, Trevor A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
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.
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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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