Whole-genome sequencing of recurrent neuroblastoma reveals somatic mutations that affect key players in cancer progression and telomere maintenance

Abstract Neuroblastoma is the most common and deadly childhood tumor. Relapsed or refractory neuroblastoma has a very poor prognosis despite recent treatment advances. To investigate genomic alterations associated with relapse and therapy resistance, whole-genome sequencing was performed on diagnost...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Susanne Fransson, Angela Martinez-Monleon, Mathias Johansson, Rose-Marie Sjöberg, Caroline Björklund, Gustaf Ljungman, Torben Ek, Per Kogner, Tommy Martinsson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/040e279adcf3445389b188aed659660d
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:040e279adcf3445389b188aed659660d
record_format	dspace
spelling	oai:doaj.org-article:040e279adcf3445389b188aed659660d2021-12-02T14:01:28ZWhole-genome sequencing of recurrent neuroblastoma reveals somatic mutations that affect key players in cancer progression and telomere maintenance10.1038/s41598-020-78370-72045-2322https://doaj.org/article/040e279adcf3445389b188aed659660d2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78370-7https://doaj.org/toc/2045-2322Abstract Neuroblastoma is the most common and deadly childhood tumor. Relapsed or refractory neuroblastoma has a very poor prognosis despite recent treatment advances. To investigate genomic alterations associated with relapse and therapy resistance, whole-genome sequencing was performed on diagnostic and relapsed lesions together with constitutional DNA from seven children. Sequencing of relapsed tumors indicates somatic alterations in diverse genes, including those involved in RAS-MAPK signaling, promoting cell cycle progression or function in telomere maintenance and immortalization. Among recurrent alterations, CCND1-gain, TERT-rearrangements, and point mutations in POLR2A, CDK5RAP, and MUC16 were shown in ≥ 2 individuals. Our cohort contained examples of converging genomic alterations in primary-relapse tumor pairs, indicating dependencies related to specific genetic lesions. We also detected rare genetic germline variants in DNA repair genes (e.g., BARD1, BRCA2, CHEK2, and WRN) that might cooperate with somatically acquired variants in these patients with highly aggressive recurrent neuroblastoma. Our data indicate the importance of monitoring recurrent neuroblastoma through sequential genomic characterization and that new therapeutic approaches combining the targeting of MAPK signaling, cell cycle progression, and telomere activity are required for this challenging patient group.Susanne FranssonAngela Martinez-MonleonMathias JohanssonRose-Marie SjöbergCaroline BjörklundGustaf LjungmanTorben EkPer KognerTommy MartinssonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Susanne Fransson Angela Martinez-Monleon Mathias Johansson Rose-Marie Sjöberg Caroline Björklund Gustaf Ljungman Torben Ek Per Kogner Tommy Martinsson Whole-genome sequencing of recurrent neuroblastoma reveals somatic mutations that affect key players in cancer progression and telomere maintenance
description	Abstract Neuroblastoma is the most common and deadly childhood tumor. Relapsed or refractory neuroblastoma has a very poor prognosis despite recent treatment advances. To investigate genomic alterations associated with relapse and therapy resistance, whole-genome sequencing was performed on diagnostic and relapsed lesions together with constitutional DNA from seven children. Sequencing of relapsed tumors indicates somatic alterations in diverse genes, including those involved in RAS-MAPK signaling, promoting cell cycle progression or function in telomere maintenance and immortalization. Among recurrent alterations, CCND1-gain, TERT-rearrangements, and point mutations in POLR2A, CDK5RAP, and MUC16 were shown in ≥ 2 individuals. Our cohort contained examples of converging genomic alterations in primary-relapse tumor pairs, indicating dependencies related to specific genetic lesions. We also detected rare genetic germline variants in DNA repair genes (e.g., BARD1, BRCA2, CHEK2, and WRN) that might cooperate with somatically acquired variants in these patients with highly aggressive recurrent neuroblastoma. Our data indicate the importance of monitoring recurrent neuroblastoma through sequential genomic characterization and that new therapeutic approaches combining the targeting of MAPK signaling, cell cycle progression, and telomere activity are required for this challenging patient group.
format	article
author	Susanne Fransson Angela Martinez-Monleon Mathias Johansson Rose-Marie Sjöberg Caroline Björklund Gustaf Ljungman Torben Ek Per Kogner Tommy Martinsson
author_facet	Susanne Fransson Angela Martinez-Monleon Mathias Johansson Rose-Marie Sjöberg Caroline Björklund Gustaf Ljungman Torben Ek Per Kogner Tommy Martinsson
author_sort	Susanne Fransson
title	Whole-genome sequencing of recurrent neuroblastoma reveals somatic mutations that affect key players in cancer progression and telomere maintenance
title_short	Whole-genome sequencing of recurrent neuroblastoma reveals somatic mutations that affect key players in cancer progression and telomere maintenance
title_full	Whole-genome sequencing of recurrent neuroblastoma reveals somatic mutations that affect key players in cancer progression and telomere maintenance
title_fullStr	Whole-genome sequencing of recurrent neuroblastoma reveals somatic mutations that affect key players in cancer progression and telomere maintenance
title_full_unstemmed	Whole-genome sequencing of recurrent neuroblastoma reveals somatic mutations that affect key players in cancer progression and telomere maintenance
title_sort	whole-genome sequencing of recurrent neuroblastoma reveals somatic mutations that affect key players in cancer progression and telomere maintenance
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/040e279adcf3445389b188aed659660d
work_keys_str_mv	AT susannefransson wholegenomesequencingofrecurrentneuroblastomarevealssomaticmutationsthataffectkeyplayersincancerprogressionandtelomeremaintenance AT angelamartinezmonleon wholegenomesequencingofrecurrentneuroblastomarevealssomaticmutationsthataffectkeyplayersincancerprogressionandtelomeremaintenance AT mathiasjohansson wholegenomesequencingofrecurrentneuroblastomarevealssomaticmutationsthataffectkeyplayersincancerprogressionandtelomeremaintenance AT rosemariesjoberg wholegenomesequencingofrecurrentneuroblastomarevealssomaticmutationsthataffectkeyplayersincancerprogressionandtelomeremaintenance AT carolinebjorklund wholegenomesequencingofrecurrentneuroblastomarevealssomaticmutationsthataffectkeyplayersincancerprogressionandtelomeremaintenance AT gustafljungman wholegenomesequencingofrecurrentneuroblastomarevealssomaticmutationsthataffectkeyplayersincancerprogressionandtelomeremaintenance AT torbenek wholegenomesequencingofrecurrentneuroblastomarevealssomaticmutationsthataffectkeyplayersincancerprogressionandtelomeremaintenance AT perkogner wholegenomesequencingofrecurrentneuroblastomarevealssomaticmutationsthataffectkeyplayersincancerprogressionandtelomeremaintenance AT tommymartinsson wholegenomesequencingofrecurrentneuroblastomarevealssomaticmutationsthataffectkeyplayersincancerprogressionandtelomeremaintenance
_version_	1718392120664915968

Whole-genome sequencing of recurrent neuroblastoma reveals somatic mutations that affect key players in cancer progression and telomere maintenance

Ejemplares similares