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Influence of segmental chromosome abnormalities on survival in children over the age of 12 months with unresectable localised peripheral neuroblastic tumours without MYCN amplification

Lookup NU author(s): Dr Nicholas Bown, Professor John LunecORCiD, Professor Deborah Tweddle

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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 the presence 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) and overall 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.


Publication metadata

Author(s): Defferrari R, Mazzocco K, Ambros IM, Ambros PF, Bedwell C, Beiske K, Benard J, Berbegall AP, Bown N, Combaret V, Couturier J, Erminio G, Gambini C, Garaventa A, Gross N, Haupt R, Kohler J, Jeison M, Lunec J, Marques B, Martinsson T, Noguera R, Parodi S, Schleiermacher G, Tweddle DA, Valent A, Van Roy N, Vicha A, Villamon E, Tonini GP

Publication type: Article

Publication status: Published

Journal: British Journal of Cancer

Year: 2015

Volume: 112

Issue: 2

Pages: 290-295

Print publication date: 20/01/2015

Online publication date: 04/11/2014

Acceptance date: 04/10/2014

ISSN (print): 0007-0920

ISSN (electronic): 1532-1827

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/bjc.2014.557

DOI: 10.1038/bjc.2014.557


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Funding

Funder referenceFunder name
Annenberg Foundation
Cancer Research UK (CRUK)
Carte d'Identite des Tumeurs programme of the Ligue Nationale Contre le Cancer
Institut National de la Sante et de la Recherche Medicale
Societe Francaise de Lutte contre les Cancers et les Leucemie de l'Enfant et de l'Adolescent (SFCE)
CCRI
Instituto Carlos III Madrid ERDF, Spain
Italian Neuroblastoma Foundation
Ligue Nationale Contre le Cancer (Equipe labellisee) the Federation Enfants et Sante
MH CZ-DRO
National Resource Centre for Childhood Solid Tumours (KSSB), Norway
Neuroblastoma Society in the UK
00064203University Hospital Motol, Prague, Czech Republic
02014PHRC AOM
13422Austrian National Bank
RD06/0020/0102RTICC
PI10/15Fundacion Asociacion Espanola contra el Cancer, FIS
RD12/0036/0020RTICC

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