Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors
Abstract 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 analyze...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Eirini Christodoulou [verfasserIn] Venkata Yellapantula [verfasserIn] Katrina O’Halloran [verfasserIn] Liya Xu [verfasserIn] Jesse L. Berry [verfasserIn] Jennifer A. Cotter [verfasserIn] Anya Zdanowicz [verfasserIn] Leo Mascarenhas [verfasserIn] James F. Amatruda [verfasserIn] Dejerianne Ostrow [verfasserIn] Moiz Bootwalla [verfasserIn] Xiaowu Gai [verfasserIn] Fariba Navid [verfasserIn] Jaclyn A. Biegel [verfasserIn] |
|---|
| Format: |
E-Artikel |
|---|---|
| Sprache: |
Englisch |
| Erschienen: |
2023 |
|---|
| Übergeordnetes Werk: |
In: npj Precision Oncology - Nature Portfolio, 2017, 7(2023), 1, Seite 11 |
|---|---|
| Übergeordnetes Werk: |
volume:7 ; year:2023 ; number:1 ; pages:11 |
| Links: |
|---|
| DOI / URN: |
10.1038/s41698-023-00357-0 |
|---|
| Katalog-ID: |
DOAJ087778920 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | DOAJ087778920 | ||
| 003 | DE-627 | ||
| 005 | 20240414102521.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 230331s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41698-023-00357-0 |2 doi | |
| 035 | |a (DE-627)DOAJ087778920 | ||
| 035 | |a (DE-599)DOAJ2d4c69443c07400f8b129c34095fae56 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 050 | 0 | |a RC254-282 | |
| 100 | 0 | |a Eirini Christodoulou |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract 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. | ||
| 653 | 0 | |a Neoplasms. Tumors. Oncology. Including cancer and carcinogens | |
| 700 | 0 | |a Venkata Yellapantula |e verfasserin |4 aut | |
| 700 | 0 | |a Katrina O’Halloran |e verfasserin |4 aut | |
| 700 | 0 | |a Liya Xu |e verfasserin |4 aut | |
| 700 | 0 | |a Jesse L. Berry |e verfasserin |4 aut | |
| 700 | 0 | |a Jennifer A. Cotter |e verfasserin |4 aut | |
| 700 | 0 | |a Anya Zdanowicz |e verfasserin |4 aut | |
| 700 | 0 | |a Leo Mascarenhas |e verfasserin |4 aut | |
| 700 | 0 | |a James F. Amatruda |e verfasserin |4 aut | |
| 700 | 0 | |a Dejerianne Ostrow |e verfasserin |4 aut | |
| 700 | 0 | |a Moiz Bootwalla |e verfasserin |4 aut | |
| 700 | 0 | |a Xiaowu Gai |e verfasserin |4 aut | |
| 700 | 0 | |a Fariba Navid |e verfasserin |4 aut | |
| 700 | 0 | |a Jaclyn A. Biegel |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i In |t npj Precision Oncology |d Nature Portfolio, 2017 |g 7(2023), 1, Seite 11 |w (DE-627)884384454 |w (DE-600)2891458-2 |x 2397768X |7 nnns |
| 773 | 1 | 8 | |g volume:7 |g year:2023 |g number:1 |g pages:11 |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41698-023-00357-0 |z kostenfrei |
| 856 | 4 | 0 | |u https://doaj.org/article/2d4c69443c07400f8b129c34095fae56 |z kostenfrei |
| 856 | 4 | 0 | |u https://doi.org/10.1038/s41698-023-00357-0 |z kostenfrei |
| 856 | 4 | 2 | |u https://doaj.org/toc/2397-768X |y Journal toc |z kostenfrei |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a SYSFLAG_A | ||
| 912 | |a GBV_DOAJ | ||
| 912 | |a GBV_ILN_20 | ||
| 912 | |a GBV_ILN_22 | ||
| 912 | |a GBV_ILN_23 | ||
| 912 | |a GBV_ILN_24 | ||
| 912 | |a GBV_ILN_39 | ||
| 912 | |a GBV_ILN_40 | ||
| 912 | |a GBV_ILN_60 | ||
| 912 | |a GBV_ILN_62 | ||
| 912 | |a GBV_ILN_63 | ||
| 912 | |a GBV_ILN_65 | ||
| 912 | |a GBV_ILN_69 | ||
| 912 | |a GBV_ILN_73 | ||
| 912 | |a GBV_ILN_74 | ||
| 912 | |a GBV_ILN_95 | ||
| 912 | |a GBV_ILN_105 | ||
| 912 | |a GBV_ILN_110 | ||
| 912 | |a GBV_ILN_151 | ||
| 912 | |a GBV_ILN_161 | ||
| 912 | |a GBV_ILN_170 | ||
| 912 | |a GBV_ILN_206 | ||
| 912 | |a GBV_ILN_213 | ||
| 912 | |a GBV_ILN_230 | ||
| 912 | |a GBV_ILN_285 | ||
| 912 | |a GBV_ILN_293 | ||
| 912 | |a GBV_ILN_602 | ||
| 912 | |a GBV_ILN_2014 | ||
| 912 | |a GBV_ILN_4012 | ||
| 912 | |a GBV_ILN_4037 | ||
| 912 | |a GBV_ILN_4112 | ||
| 912 | |a GBV_ILN_4125 | ||
| 912 | |a GBV_ILN_4126 | ||
| 912 | |a GBV_ILN_4249 | ||
| 912 | |a GBV_ILN_4305 | ||
| 912 | |a GBV_ILN_4306 | ||
| 912 | |a GBV_ILN_4307 | ||
| 912 | |a GBV_ILN_4313 | ||
| 912 | |a GBV_ILN_4322 | ||
| 912 | |a GBV_ILN_4323 | ||
| 912 | |a GBV_ILN_4324 | ||
| 912 | |a GBV_ILN_4325 | ||
| 912 | |a GBV_ILN_4338 | ||
| 912 | |a GBV_ILN_4367 | ||
| 912 | |a GBV_ILN_4700 | ||
| 951 | |a AR | ||
| 952 | |d 7 |j 2023 |e 1 |h 11 | ||
| author_variant |
e c ec v y vy k o ko l x lx j l b jlb j a c jac a z az l m lm j f a jfa d o do m b mb x g xg f n fn j a b jab |
|---|---|
| matchkey_str |
article:2397768X:2023----::obndopswoeeoentreesqecnilqibose |
| hierarchy_sort_str |
2023 |
| callnumber-subject-code |
RC |
| publishDate |
2023 |
| allfields |
10.1038/s41698-023-00357-0 doi (DE-627)DOAJ087778920 (DE-599)DOAJ2d4c69443c07400f8b129c34095fae56 DE-627 ger DE-627 rakwb eng RC254-282 Eirini Christodoulou verfasserin aut Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Venkata Yellapantula verfasserin aut Katrina O’Halloran verfasserin aut Liya Xu verfasserin aut Jesse L. Berry verfasserin aut Jennifer A. Cotter verfasserin aut Anya Zdanowicz verfasserin aut Leo Mascarenhas verfasserin aut James F. Amatruda verfasserin aut Dejerianne Ostrow verfasserin aut Moiz Bootwalla verfasserin aut Xiaowu Gai verfasserin aut Fariba Navid verfasserin aut Jaclyn A. Biegel verfasserin aut In npj Precision Oncology Nature Portfolio, 2017 7(2023), 1, Seite 11 (DE-627)884384454 (DE-600)2891458-2 2397768X nnns volume:7 year:2023 number:1 pages:11 https://doi.org/10.1038/s41698-023-00357-0 kostenfrei https://doaj.org/article/2d4c69443c07400f8b129c34095fae56 kostenfrei https://doi.org/10.1038/s41698-023-00357-0 kostenfrei https://doaj.org/toc/2397-768X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2023 1 11 |
| spelling |
10.1038/s41698-023-00357-0 doi (DE-627)DOAJ087778920 (DE-599)DOAJ2d4c69443c07400f8b129c34095fae56 DE-627 ger DE-627 rakwb eng RC254-282 Eirini Christodoulou verfasserin aut Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Venkata Yellapantula verfasserin aut Katrina O’Halloran verfasserin aut Liya Xu verfasserin aut Jesse L. Berry verfasserin aut Jennifer A. Cotter verfasserin aut Anya Zdanowicz verfasserin aut Leo Mascarenhas verfasserin aut James F. Amatruda verfasserin aut Dejerianne Ostrow verfasserin aut Moiz Bootwalla verfasserin aut Xiaowu Gai verfasserin aut Fariba Navid verfasserin aut Jaclyn A. Biegel verfasserin aut In npj Precision Oncology Nature Portfolio, 2017 7(2023), 1, Seite 11 (DE-627)884384454 (DE-600)2891458-2 2397768X nnns volume:7 year:2023 number:1 pages:11 https://doi.org/10.1038/s41698-023-00357-0 kostenfrei https://doaj.org/article/2d4c69443c07400f8b129c34095fae56 kostenfrei https://doi.org/10.1038/s41698-023-00357-0 kostenfrei https://doaj.org/toc/2397-768X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2023 1 11 |
| allfields_unstemmed |
10.1038/s41698-023-00357-0 doi (DE-627)DOAJ087778920 (DE-599)DOAJ2d4c69443c07400f8b129c34095fae56 DE-627 ger DE-627 rakwb eng RC254-282 Eirini Christodoulou verfasserin aut Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Venkata Yellapantula verfasserin aut Katrina O’Halloran verfasserin aut Liya Xu verfasserin aut Jesse L. Berry verfasserin aut Jennifer A. Cotter verfasserin aut Anya Zdanowicz verfasserin aut Leo Mascarenhas verfasserin aut James F. Amatruda verfasserin aut Dejerianne Ostrow verfasserin aut Moiz Bootwalla verfasserin aut Xiaowu Gai verfasserin aut Fariba Navid verfasserin aut Jaclyn A. Biegel verfasserin aut In npj Precision Oncology Nature Portfolio, 2017 7(2023), 1, Seite 11 (DE-627)884384454 (DE-600)2891458-2 2397768X nnns volume:7 year:2023 number:1 pages:11 https://doi.org/10.1038/s41698-023-00357-0 kostenfrei https://doaj.org/article/2d4c69443c07400f8b129c34095fae56 kostenfrei https://doi.org/10.1038/s41698-023-00357-0 kostenfrei https://doaj.org/toc/2397-768X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2023 1 11 |
| allfieldsGer |
10.1038/s41698-023-00357-0 doi (DE-627)DOAJ087778920 (DE-599)DOAJ2d4c69443c07400f8b129c34095fae56 DE-627 ger DE-627 rakwb eng RC254-282 Eirini Christodoulou verfasserin aut Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Venkata Yellapantula verfasserin aut Katrina O’Halloran verfasserin aut Liya Xu verfasserin aut Jesse L. Berry verfasserin aut Jennifer A. Cotter verfasserin aut Anya Zdanowicz verfasserin aut Leo Mascarenhas verfasserin aut James F. Amatruda verfasserin aut Dejerianne Ostrow verfasserin aut Moiz Bootwalla verfasserin aut Xiaowu Gai verfasserin aut Fariba Navid verfasserin aut Jaclyn A. Biegel verfasserin aut In npj Precision Oncology Nature Portfolio, 2017 7(2023), 1, Seite 11 (DE-627)884384454 (DE-600)2891458-2 2397768X nnns volume:7 year:2023 number:1 pages:11 https://doi.org/10.1038/s41698-023-00357-0 kostenfrei https://doaj.org/article/2d4c69443c07400f8b129c34095fae56 kostenfrei https://doi.org/10.1038/s41698-023-00357-0 kostenfrei https://doaj.org/toc/2397-768X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2023 1 11 |
| allfieldsSound |
10.1038/s41698-023-00357-0 doi (DE-627)DOAJ087778920 (DE-599)DOAJ2d4c69443c07400f8b129c34095fae56 DE-627 ger DE-627 rakwb eng RC254-282 Eirini Christodoulou verfasserin aut Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract 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. Neoplasms. Tumors. Oncology. Including cancer and carcinogens Venkata Yellapantula verfasserin aut Katrina O’Halloran verfasserin aut Liya Xu verfasserin aut Jesse L. Berry verfasserin aut Jennifer A. Cotter verfasserin aut Anya Zdanowicz verfasserin aut Leo Mascarenhas verfasserin aut James F. Amatruda verfasserin aut Dejerianne Ostrow verfasserin aut Moiz Bootwalla verfasserin aut Xiaowu Gai verfasserin aut Fariba Navid verfasserin aut Jaclyn A. Biegel verfasserin aut In npj Precision Oncology Nature Portfolio, 2017 7(2023), 1, Seite 11 (DE-627)884384454 (DE-600)2891458-2 2397768X nnns volume:7 year:2023 number:1 pages:11 https://doi.org/10.1038/s41698-023-00357-0 kostenfrei https://doaj.org/article/2d4c69443c07400f8b129c34095fae56 kostenfrei https://doi.org/10.1038/s41698-023-00357-0 kostenfrei https://doaj.org/toc/2397-768X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2023 1 11 |
| language |
English |
| source |
In npj Precision Oncology 7(2023), 1, Seite 11 volume:7 year:2023 number:1 pages:11 |
| sourceStr |
In npj Precision Oncology 7(2023), 1, Seite 11 volume:7 year:2023 number:1 pages:11 |
| format_phy_str_mv |
Article |
| institution |
findex.gbv.de |
| topic_facet |
Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| isfreeaccess_bool |
true |
| container_title |
npj Precision Oncology |
| authorswithroles_txt_mv |
Eirini Christodoulou @@aut@@ Venkata Yellapantula @@aut@@ Katrina O’Halloran @@aut@@ Liya Xu @@aut@@ Jesse L. Berry @@aut@@ Jennifer A. Cotter @@aut@@ Anya Zdanowicz @@aut@@ Leo Mascarenhas @@aut@@ James F. Amatruda @@aut@@ Dejerianne Ostrow @@aut@@ Moiz Bootwalla @@aut@@ Xiaowu Gai @@aut@@ Fariba Navid @@aut@@ Jaclyn A. Biegel @@aut@@ |
| publishDateDaySort_date |
2023-01-01T00:00:00Z |
| hierarchy_top_id |
884384454 |
| id |
DOAJ087778920 |
| language_de |
englisch |
| fullrecord |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ087778920</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240414102521.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230331s2023 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1038/s41698-023-00357-0</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ087778920</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ2d4c69443c07400f8b129c34095fae56</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC254-282</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Eirini Christodoulou</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2023</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract 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.</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Neoplasms. Tumors. Oncology. Including cancer and carcinogens</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Venkata Yellapantula</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Katrina O’Halloran</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Liya Xu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jesse L. Berry</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jennifer A. Cotter</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Anya Zdanowicz</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Leo Mascarenhas</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">James F. Amatruda</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Dejerianne Ostrow</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Moiz Bootwalla</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Xiaowu Gai</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Fariba Navid</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jaclyn A. Biegel</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">npj Precision Oncology</subfield><subfield code="d">Nature Portfolio, 2017</subfield><subfield code="g">7(2023), 1, Seite 11</subfield><subfield code="w">(DE-627)884384454</subfield><subfield code="w">(DE-600)2891458-2</subfield><subfield code="x">2397768X</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:7</subfield><subfield code="g">year:2023</subfield><subfield code="g">number:1</subfield><subfield code="g">pages:11</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1038/s41698-023-00357-0</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/2d4c69443c07400f8b129c34095fae56</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1038/s41698-023-00357-0</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/2397-768X</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">7</subfield><subfield code="j">2023</subfield><subfield code="e">1</subfield><subfield code="h">11</subfield></datafield></record></collection>
|
| callnumber-first |
R - Medicine |
| author |
Eirini Christodoulou |
| spellingShingle |
Eirini Christodoulou misc RC254-282 misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors |
| authorStr |
Eirini Christodoulou |
| ppnlink_with_tag_str_mv |
@@773@@(DE-627)884384454 |
| format |
electronic Article |
| delete_txt_mv |
keep |
| author_role |
aut aut aut aut aut aut aut aut aut aut aut aut aut aut |
| collection |
DOAJ |
| remote_str |
true |
| callnumber-label |
RC254-282 |
| illustrated |
Not Illustrated |
| issn |
2397768X |
| topic_title |
RC254-282 Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors |
| topic |
misc RC254-282 misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| topic_unstemmed |
misc RC254-282 misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| topic_browse |
misc RC254-282 misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| format_facet |
Elektronische Aufsätze Aufsätze Elektronische Ressource |
| format_main_str_mv |
Text Zeitschrift/Artikel |
| carriertype_str_mv |
cr |
| hierarchy_parent_title |
npj Precision Oncology |
| hierarchy_parent_id |
884384454 |
| hierarchy_top_title |
npj Precision Oncology |
| isfreeaccess_txt |
true |
| familylinks_str_mv |
(DE-627)884384454 (DE-600)2891458-2 |
| title |
Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors |
| ctrlnum |
(DE-627)DOAJ087778920 (DE-599)DOAJ2d4c69443c07400f8b129c34095fae56 |
| title_full |
Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors |
| author_sort |
Eirini Christodoulou |
| journal |
npj Precision Oncology |
| journalStr |
npj Precision Oncology |
| callnumber-first-code |
R |
| lang_code |
eng |
| isOA_bool |
true |
| recordtype |
marc |
| publishDateSort |
2023 |
| contenttype_str_mv |
txt |
| container_start_page |
11 |
| author_browse |
Eirini Christodoulou Venkata Yellapantula Katrina O’Halloran Liya Xu Jesse L. Berry Jennifer A. Cotter Anya Zdanowicz Leo Mascarenhas James F. Amatruda Dejerianne Ostrow Moiz Bootwalla Xiaowu Gai Fariba Navid Jaclyn A. Biegel |
| container_volume |
7 |
| class |
RC254-282 |
| format_se |
Elektronische Aufsätze |
| author-letter |
Eirini Christodoulou |
| doi_str_mv |
10.1038/s41698-023-00357-0 |
| author2-role |
verfasserin |
| title_sort |
combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors |
| callnumber |
RC254-282 |
| title_auth |
Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors |
| abstract |
Abstract 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. |
| abstractGer |
Abstract 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. |
| abstract_unstemmed |
Abstract 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. |
| collection_details |
GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 |
| container_issue |
1 |
| title_short |
Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors |
| url |
https://doi.org/10.1038/s41698-023-00357-0 https://doaj.org/article/2d4c69443c07400f8b129c34095fae56 https://doaj.org/toc/2397-768X |
| remote_bool |
true |
| author2 |
Venkata Yellapantula Katrina O’Halloran Liya Xu Jesse L. Berry Jennifer A. Cotter Anya Zdanowicz Leo Mascarenhas James F. Amatruda Dejerianne Ostrow Moiz Bootwalla Xiaowu Gai Fariba Navid Jaclyn A. Biegel |
| author2Str |
Venkata Yellapantula Katrina O’Halloran Liya Xu Jesse L. Berry Jennifer A. Cotter Anya Zdanowicz Leo Mascarenhas James F. Amatruda Dejerianne Ostrow Moiz Bootwalla Xiaowu Gai Fariba Navid Jaclyn A. Biegel |
| ppnlink |
884384454 |
| callnumber-subject |
RC - Internal Medicine |
| mediatype_str_mv |
c |
| isOA_txt |
true |
| hochschulschrift_bool |
false |
| doi_str |
10.1038/s41698-023-00357-0 |
| callnumber-a |
RC254-282 |
| up_date |
2024-07-03T13:55:34.138Z |
| _version_ |
1803566379582881792 |
| fullrecord_marcxml |
<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ087778920</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240414102521.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230331s2023 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1038/s41698-023-00357-0</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ087778920</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ2d4c69443c07400f8b129c34095fae56</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RC254-282</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Eirini Christodoulou</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Combined low-pass whole genome and targeted sequencing in liquid biopsies for pediatric solid tumors</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2023</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract 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.</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Neoplasms. Tumors. Oncology. Including cancer and carcinogens</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Venkata Yellapantula</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Katrina O’Halloran</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Liya Xu</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jesse L. Berry</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jennifer A. Cotter</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Anya Zdanowicz</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Leo Mascarenhas</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">James F. Amatruda</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Dejerianne Ostrow</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Moiz Bootwalla</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Xiaowu Gai</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Fariba Navid</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="0" ind2=" "><subfield code="a">Jaclyn A. Biegel</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">In</subfield><subfield code="t">npj Precision Oncology</subfield><subfield code="d">Nature Portfolio, 2017</subfield><subfield code="g">7(2023), 1, Seite 11</subfield><subfield code="w">(DE-627)884384454</subfield><subfield code="w">(DE-600)2891458-2</subfield><subfield code="x">2397768X</subfield><subfield code="7">nnns</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:7</subfield><subfield code="g">year:2023</subfield><subfield code="g">number:1</subfield><subfield code="g">pages:11</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1038/s41698-023-00357-0</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doaj.org/article/2d4c69443c07400f8b129c34095fae56</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1038/s41698-023-00357-0</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="u">https://doaj.org/toc/2397-768X</subfield><subfield code="y">Journal toc</subfield><subfield code="z">kostenfrei</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_A</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_DOAJ</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_20</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_23</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_24</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_39</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_60</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_62</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_63</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_65</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_69</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_73</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_74</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_95</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_110</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_151</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_161</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_170</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_206</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_213</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_230</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_285</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_293</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_602</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_2014</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4012</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4037</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4112</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4125</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4126</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4249</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4305</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4306</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4307</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4313</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4322</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4323</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4324</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4325</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4338</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4367</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_4700</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">7</subfield><subfield code="j">2023</subfield><subfield code="e">1</subfield><subfield code="h">11</subfield></datafield></record></collection>
|
| score |
7.4014397 |