Genomics

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Genomic profiles of unresectable localized peripheral neuroblastic tumours without MYCN amplificatioun of children over the age of 12 months


ABSTRACT: Background: The prognostic impact of segmental chromosome alterations (SCAs) in children older than 1 year, diagnosed with localised unresectable neuroblastoma (NB) without MYCN amplification enrolled in the European Unresectable Neuroblastoma (EUNB) protocol is still to be clarified, while, for other group of patients, the presence of SCAs is associated with poor prognosis. Methods: To understand the role of SCAs we performed multilocus/pangenomic analysis of 98 tumour samples from patients enrolled in the EUNB protocol. Results: Age at diagnosis was categorised into two groups using 18 months as the age cutoff. Significant difference in thepresence of SCAs was seen in tumours of patients between 12 and 18 months and over 18 months of age at diagnosis, respectively (P<0.04). A significant correlation (P<0.03) was observed between number of SCAs per tumour and age. Event-free (EFS) andoverall survival (OS) were calculated in both age groups, according to both the presence and number of SCAs. In older patients, a poorer survival was associated with the presence of SCAs (EFS<46% vs 75%, P<0.023; OS<66.8% vs 100%, P<0.003). Moreover, OS of older patients inversely correlated with number of SCAs (P<0.002). Finally, SCAs provided additional prognostic information beyond histoprognosis, as their presence was associated with poorer OS in patients over 18 months with unfavourable International Neuroblastoma Pathology Classification (INPC) histopathology (P<0.018). Conclusions: The presence of SCAs is a negative prognostic marker that impairs outcome of patients over the age of 18 months with localised unresectable NB without MYCN amplification, especially when more than one SCA is present. Moreover, in older patients with unfavourable INPC tumour histoprognosis, the presence of SCAs significantly affects OS.

ORGANISM(S): Homo sapiens

PROVIDER: GSE112173 | GEO | 2018/03/22

REPOSITORIES: GEO

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