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Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors

We designed a liquid biopsy (LB) platform employing low-pass whole genome sequencing (LP-WGS) and targeted sequencing of cell-free (cf) DNA from plasma to detect genome-wide copy number alterations (CNAs) and gene fusions in pediatric solid tumors. A total of 143 plasma samples were analyzed from 19...

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Autores principales: Christodoulou, Eirini, Yellapantula, Venkata, O’Halloran, Katrina, Xu, Liya, Berry, Jesse L., Cotter, Jennifer A., Zdanowicz, Anya, Mascarenhas, Leo, Amatruda, James F., Ostrow, Dejerianne, Bootwalla, Moiz, Gai, Xiaowu, Navid, Fariba, Biegel, Jaclyn A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9941464/
https://www.ncbi.nlm.nih.gov/pubmed/36805676
http://dx.doi.org/10.1038/s41698-023-00357-0
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author Christodoulou, Eirini
Yellapantula, Venkata
O’Halloran, Katrina
Xu, Liya
Berry, Jesse L.
Cotter, Jennifer A.
Zdanowicz, Anya
Mascarenhas, Leo
Amatruda, James F.
Ostrow, Dejerianne
Bootwalla, Moiz
Gai, Xiaowu
Navid, Fariba
Biegel, Jaclyn A.
author_facet Christodoulou, Eirini
Yellapantula, Venkata
O’Halloran, Katrina
Xu, Liya
Berry, Jesse L.
Cotter, Jennifer A.
Zdanowicz, Anya
Mascarenhas, Leo
Amatruda, James F.
Ostrow, Dejerianne
Bootwalla, Moiz
Gai, Xiaowu
Navid, Fariba
Biegel, Jaclyn A.
author_sort Christodoulou, Eirini
collection PubMed
description We designed a liquid biopsy (LB) platform employing low-pass whole genome sequencing (LP-WGS) and targeted sequencing of cell-free (cf) DNA from plasma to detect genome-wide copy number alterations (CNAs) and gene fusions in pediatric solid tumors. A total of 143 plasma samples were analyzed from 19 controls and 73 patients, including 44 bone or soft-tissue sarcomas and 12 renal, 10 germ cell, five hepatic, and two thyroid tumors. cfDNA was isolated from plasma collected at diagnosis, during and after therapy, and/or at relapse. Twenty-six of 37 (70%) patients enrolled at diagnosis without prior therapy (radiation, surgery, or chemotherapy) had circulating tumor DNA (ctDNA), based on the detection of CNAs from LP-WGS, including 18 of 27 (67%) patients with localized disease and eight of 10 (80%) patients with metastatic disease. None of the controls had detectable somatic CNAs. There was a high concordance of CNAs identified by LP-WGS to CNAs detected by chromosomal microarray analysis in the matching tumors. Mutations identified in tumor samples with our next-generation sequencing (NGS) panel, OncoKids®, were also detected by LP-WGS of ctDNA in 14 of 26 plasma samples. Finally, we developed a hybridization-based capture panel to target EWSR1 and FOXO1 fusions from patients with Ewing sarcoma or alveolar rhabdomyosarcoma (ARMS), respectively. Fusions were detected in the plasma from 10 of 12 patients with Ewing sarcoma and in two of two patients with ARMS. Combined, these data demonstrate the clinical applicability of our LB platform to evaluate pediatric patients with a variety of solid tumors.
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spelling pubmed-99414642023-02-22 Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors Christodoulou, Eirini Yellapantula, Venkata O’Halloran, Katrina Xu, Liya Berry, Jesse L. Cotter, Jennifer A. Zdanowicz, Anya Mascarenhas, Leo Amatruda, James F. Ostrow, Dejerianne Bootwalla, Moiz Gai, Xiaowu Navid, Fariba Biegel, Jaclyn A. NPJ Precis Oncol Article We designed a liquid biopsy (LB) platform employing low-pass whole genome sequencing (LP-WGS) and targeted sequencing of cell-free (cf) DNA from plasma to detect genome-wide copy number alterations (CNAs) and gene fusions in pediatric solid tumors. A total of 143 plasma samples were analyzed from 19 controls and 73 patients, including 44 bone or soft-tissue sarcomas and 12 renal, 10 germ cell, five hepatic, and two thyroid tumors. cfDNA was isolated from plasma collected at diagnosis, during and after therapy, and/or at relapse. Twenty-six of 37 (70%) patients enrolled at diagnosis without prior therapy (radiation, surgery, or chemotherapy) had circulating tumor DNA (ctDNA), based on the detection of CNAs from LP-WGS, including 18 of 27 (67%) patients with localized disease and eight of 10 (80%) patients with metastatic disease. None of the controls had detectable somatic CNAs. There was a high concordance of CNAs identified by LP-WGS to CNAs detected by chromosomal microarray analysis in the matching tumors. Mutations identified in tumor samples with our next-generation sequencing (NGS) panel, OncoKids®, were also detected by LP-WGS of ctDNA in 14 of 26 plasma samples. Finally, we developed a hybridization-based capture panel to target EWSR1 and FOXO1 fusions from patients with Ewing sarcoma or alveolar rhabdomyosarcoma (ARMS), respectively. Fusions were detected in the plasma from 10 of 12 patients with Ewing sarcoma and in two of two patients with ARMS. Combined, these data demonstrate the clinical applicability of our LB platform to evaluate pediatric patients with a variety of solid tumors. Nature Publishing Group UK 2023-02-20 /pmc/articles/PMC9941464/ /pubmed/36805676 http://dx.doi.org/10.1038/s41698-023-00357-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Christodoulou, Eirini
Yellapantula, Venkata
O’Halloran, Katrina
Xu, Liya
Berry, Jesse L.
Cotter, Jennifer A.
Zdanowicz, Anya
Mascarenhas, Leo
Amatruda, James F.
Ostrow, Dejerianne
Bootwalla, Moiz
Gai, Xiaowu
Navid, Fariba
Biegel, Jaclyn A.
Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors
title Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors
title_full Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors
title_fullStr Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors
title_full_unstemmed Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors
title_short Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors
title_sort combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9941464/
https://www.ncbi.nlm.nih.gov/pubmed/36805676
http://dx.doi.org/10.1038/s41698-023-00357-0
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