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MYCN amplification plus 1p36 loss of heterozygosity predicts ultra high risk in bone marrow metastatic neuroblastoma

BACKGROUND: This study aimed to better understand the prognostic effect of multiple genetic markers and identify more subpopulations at ultra high risk of poor outcome in bone marrow (BM) metastatic neuroblastoma (NB). METHODS: We screened the MYCN, 1p36 and 11q23 loss of heterozygosity (LOH) status...

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Autores principales: Yue, Zhi‐Xia, Xing, Tian‐Yu, Zhao, Wen, Zhao, Qian, Wang, Xi‐Si, Su, Yan, Gao, Chao, Liu, Shu‐Guang, Ma, Xiao‐Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9041068/
https://www.ncbi.nlm.nih.gov/pubmed/35137546
http://dx.doi.org/10.1002/cam4.4583
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author Yue, Zhi‐Xia
Xing, Tian‐Yu
Zhao, Wen
Zhao, Qian
Wang, Xi‐Si
Su, Yan
Gao, Chao
Liu, Shu‐Guang
Ma, Xiao‐Li
author_facet Yue, Zhi‐Xia
Xing, Tian‐Yu
Zhao, Wen
Zhao, Qian
Wang, Xi‐Si
Su, Yan
Gao, Chao
Liu, Shu‐Guang
Ma, Xiao‐Li
author_sort Yue, Zhi‐Xia
collection PubMed
description BACKGROUND: This study aimed to better understand the prognostic effect of multiple genetic markers and identify more subpopulations at ultra high risk of poor outcome in bone marrow (BM) metastatic neuroblastoma (NB). METHODS: We screened the MYCN, 1p36 and 11q23 loss of heterozygosity (LOH) statuses of 154 patients by interphase fluorescence in situ hybridization of BM cells. The clinical characteristics of patients with the three markers and their associations with prognosis were analysed. RESULTS: MYCN amplification and LOH at 1p36 and 11q23 were identified in 16.2%, 33.1% and 30.5% of patients, respectively. There were strong associations between MYCN amplification and 1p36 LOH as well as 11q23 LOH. Both MYCN amplification and 1p36 LOH were strongly associated with high levels of lactate dehydrogenase (LDH) and neuron‐specific enolase, more than 3 metastatic organs, and more events. 11q23 LOH occurred mainly in patients older than 18 months, and those who had high LDH levels. In univariate analysis, patients with MYCN amplification had poorer prognosis than those without. Patients with 1p36 LOH had a 3‐year event‐free survival (EFS) and overall survival lower than those without. 11q23 LOH was associated with poorer EFS only for patients without MYCN amplification. In a multivariate model, MYCN amplification was independently associated with decreased EFS in all cohorts. 11q23 LOH was an independent prognostic factor for patients without MYCN amplification, whereas 1p36 LOH was not an independent marker regardless of MYCN amplification. Compared with all cohorts, patients with both MYCN amplification and 1p36 LOH had the worst outcome and clinical features. CONCLUSIONS: Patients with both MYCN amplification and 1p36LOH had the worst survival rate, indicating an ultra high‐risk group. Our results may be applied in clinical practice for accurate risk stratification in future studies.
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spelling pubmed-90410682022-04-28 MYCN amplification plus 1p36 loss of heterozygosity predicts ultra high risk in bone marrow metastatic neuroblastoma Yue, Zhi‐Xia Xing, Tian‐Yu Zhao, Wen Zhao, Qian Wang, Xi‐Si Su, Yan Gao, Chao Liu, Shu‐Guang Ma, Xiao‐Li Cancer Med Clinical Cancer Research BACKGROUND: This study aimed to better understand the prognostic effect of multiple genetic markers and identify more subpopulations at ultra high risk of poor outcome in bone marrow (BM) metastatic neuroblastoma (NB). METHODS: We screened the MYCN, 1p36 and 11q23 loss of heterozygosity (LOH) statuses of 154 patients by interphase fluorescence in situ hybridization of BM cells. The clinical characteristics of patients with the three markers and their associations with prognosis were analysed. RESULTS: MYCN amplification and LOH at 1p36 and 11q23 were identified in 16.2%, 33.1% and 30.5% of patients, respectively. There were strong associations between MYCN amplification and 1p36 LOH as well as 11q23 LOH. Both MYCN amplification and 1p36 LOH were strongly associated with high levels of lactate dehydrogenase (LDH) and neuron‐specific enolase, more than 3 metastatic organs, and more events. 11q23 LOH occurred mainly in patients older than 18 months, and those who had high LDH levels. In univariate analysis, patients with MYCN amplification had poorer prognosis than those without. Patients with 1p36 LOH had a 3‐year event‐free survival (EFS) and overall survival lower than those without. 11q23 LOH was associated with poorer EFS only for patients without MYCN amplification. In a multivariate model, MYCN amplification was independently associated with decreased EFS in all cohorts. 11q23 LOH was an independent prognostic factor for patients without MYCN amplification, whereas 1p36 LOH was not an independent marker regardless of MYCN amplification. Compared with all cohorts, patients with both MYCN amplification and 1p36 LOH had the worst outcome and clinical features. CONCLUSIONS: Patients with both MYCN amplification and 1p36LOH had the worst survival rate, indicating an ultra high‐risk group. Our results may be applied in clinical practice for accurate risk stratification in future studies. John Wiley and Sons Inc. 2022-02-09 /pmc/articles/PMC9041068/ /pubmed/35137546 http://dx.doi.org/10.1002/cam4.4583 Text en © 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Clinical Cancer Research
Yue, Zhi‐Xia
Xing, Tian‐Yu
Zhao, Wen
Zhao, Qian
Wang, Xi‐Si
Su, Yan
Gao, Chao
Liu, Shu‐Guang
Ma, Xiao‐Li
MYCN amplification plus 1p36 loss of heterozygosity predicts ultra high risk in bone marrow metastatic neuroblastoma
title MYCN amplification plus 1p36 loss of heterozygosity predicts ultra high risk in bone marrow metastatic neuroblastoma
title_full MYCN amplification plus 1p36 loss of heterozygosity predicts ultra high risk in bone marrow metastatic neuroblastoma
title_fullStr MYCN amplification plus 1p36 loss of heterozygosity predicts ultra high risk in bone marrow metastatic neuroblastoma
title_full_unstemmed MYCN amplification plus 1p36 loss of heterozygosity predicts ultra high risk in bone marrow metastatic neuroblastoma
title_short MYCN amplification plus 1p36 loss of heterozygosity predicts ultra high risk in bone marrow metastatic neuroblastoma
title_sort mycn amplification plus 1p36 loss of heterozygosity predicts ultra high risk in bone marrow metastatic neuroblastoma
topic Clinical Cancer Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9041068/
https://www.ncbi.nlm.nih.gov/pubmed/35137546
http://dx.doi.org/10.1002/cam4.4583
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