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Imbalance between genomic gain and loss identifies high-risk neuroblastoma patients with worse outcomes

Survival in high-risk neuroblastoma (HR-NB) patients remains poor despite multimodal treatment. We aimed to identify HR-NB patients with worse outcomes by analyzing the genomic instability derived from segmental chromosomal aberrations. We calculated 3 genomic instability indexes for primary tumor S...

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Autores principales: Fernández-Blanco, Beatriz, Berbegall, Ana Pilar, Martin-Vañó, Susana, Castel, Victoria, Navarro, Samuel, Noguera, Rosa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674617/
https://www.ncbi.nlm.nih.gov/pubmed/33190090
http://dx.doi.org/10.1016/j.neo.2020.11.001
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author Fernández-Blanco, Beatriz
Berbegall, Ana Pilar
Martin-Vañó, Susana
Castel, Victoria
Navarro, Samuel
Noguera, Rosa
author_facet Fernández-Blanco, Beatriz
Berbegall, Ana Pilar
Martin-Vañó, Susana
Castel, Victoria
Navarro, Samuel
Noguera, Rosa
author_sort Fernández-Blanco, Beatriz
collection PubMed
description Survival in high-risk neuroblastoma (HR-NB) patients remains poor despite multimodal treatment. We aimed to identify HR-NB patients with worse outcomes by analyzing the genomic instability derived from segmental chromosomal aberrations. We calculated 3 genomic instability indexes for primary tumor SNP array profiles from 127 HR-NB patients: (1) Copy number aberration burden (%gains(length)+%losses(length)), (2) copy number load (CNL) (%gains(length)-%losses(length)) and (3) net genomic load (NGL) (%gains(amount)-%losses(amount)). Tumors were classified according to positive or negative CNL and NGL genomic subtypes. The impact of the genomic instability indexes on overall survival (OS) was assessed with Cox regression. We identified 38% of HR-NB patients with poor 5-year OS. A negative CNL genomic background was related to poor prognosis in patients ≥18 months showing tumors with homogeneous MYCN amplification (9.5% survival probability, P < 0.05) and patients with non-MYCN amplified NB (18.8% survival probability related to >2.4% CNL, P < 0.01). A positive CNL genomic background was associated with worse outcome in patients with heterogeneous MYCN amplification (22.5% survival probability, P < 0.05). We conclude that characterizing a tumor genomic background according to predominance of genome gained or lost contributes toward improved outcome prediction and brings greater insight into the tumor biology of HR-NB patients.
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spelling pubmed-76746172020-12-07 Imbalance between genomic gain and loss identifies high-risk neuroblastoma patients with worse outcomes Fernández-Blanco, Beatriz Berbegall, Ana Pilar Martin-Vañó, Susana Castel, Victoria Navarro, Samuel Noguera, Rosa Neoplasia Original article Survival in high-risk neuroblastoma (HR-NB) patients remains poor despite multimodal treatment. We aimed to identify HR-NB patients with worse outcomes by analyzing the genomic instability derived from segmental chromosomal aberrations. We calculated 3 genomic instability indexes for primary tumor SNP array profiles from 127 HR-NB patients: (1) Copy number aberration burden (%gains(length)+%losses(length)), (2) copy number load (CNL) (%gains(length)-%losses(length)) and (3) net genomic load (NGL) (%gains(amount)-%losses(amount)). Tumors were classified according to positive or negative CNL and NGL genomic subtypes. The impact of the genomic instability indexes on overall survival (OS) was assessed with Cox regression. We identified 38% of HR-NB patients with poor 5-year OS. A negative CNL genomic background was related to poor prognosis in patients ≥18 months showing tumors with homogeneous MYCN amplification (9.5% survival probability, P < 0.05) and patients with non-MYCN amplified NB (18.8% survival probability related to >2.4% CNL, P < 0.01). A positive CNL genomic background was associated with worse outcome in patients with heterogeneous MYCN amplification (22.5% survival probability, P < 0.05). We conclude that characterizing a tumor genomic background according to predominance of genome gained or lost contributes toward improved outcome prediction and brings greater insight into the tumor biology of HR-NB patients. Neoplasia Press 2020-11-13 /pmc/articles/PMC7674617/ /pubmed/33190090 http://dx.doi.org/10.1016/j.neo.2020.11.001 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Original article
Fernández-Blanco, Beatriz
Berbegall, Ana Pilar
Martin-Vañó, Susana
Castel, Victoria
Navarro, Samuel
Noguera, Rosa
Imbalance between genomic gain and loss identifies high-risk neuroblastoma patients with worse outcomes
title Imbalance between genomic gain and loss identifies high-risk neuroblastoma patients with worse outcomes
title_full Imbalance between genomic gain and loss identifies high-risk neuroblastoma patients with worse outcomes
title_fullStr Imbalance between genomic gain and loss identifies high-risk neuroblastoma patients with worse outcomes
title_full_unstemmed Imbalance between genomic gain and loss identifies high-risk neuroblastoma patients with worse outcomes
title_short Imbalance between genomic gain and loss identifies high-risk neuroblastoma patients with worse outcomes
title_sort imbalance between genomic gain and loss identifies high-risk neuroblastoma patients with worse outcomes
topic Original article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674617/
https://www.ncbi.nlm.nih.gov/pubmed/33190090
http://dx.doi.org/10.1016/j.neo.2020.11.001
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