WT1 expression is inversely correlated with MYCN amplification or expression and associated with poor survival in non-MYCN-amplified neuroblastoma.
Neuroblastoma (NB) is the most common extra cranial solid tumor in childhood and the most frequently diagnosed neoplasm during infancy. A striking feature of this tumor is its clinical heterogeneity. Several tumor progression markers have been delineated so far, among which MYCN amplification, which occurs in about 25% of total NB cases, with the percentage increasing to 30% in advanced stage NB. Although MYCN amplification is strongly correlated with NB of poor outcome, the MYCN status cannot alone predict all cases of poor survival in NB. Indeed NB without MYCN amplification (about 70-80% of NB) are not always favorable. WT1 was initially identified as a tumor suppressor gene involved in the development of a pediatric renal tumor (Wilms' tumor). Here, we describe an inverse correlation between WT1 expression and MYCN amplification and expression. However and most notably, our results show that WT1 gene expression is associated with a poor outcome for patients showing non-MYCN-amplified tumors. Thus WT1 expression is clinically significant in NB and may be a prognostic marker for better risk stratification and for an optimized therapeutic management of NB.
INSERM UMR-S 1007, Cellular Homeostasis and Cancer, Paris, France; Université Paris-Descartes, Paris Sorbonne Cité, Paris, France.
Caroline
C
Masserot
INSERM UMR-S 1007, Cellular Homeostasis and Cancer, Paris, France; Université Paris-Descartes, Paris Sorbonne Cité, Paris, France.
Qingyuan
Q
Liu
INSERM UMR-S 1007, Cellular Homeostasis and Cancer, Paris, France; Université Paris-Descartes, Paris Sorbonne Cité, Paris, France.
Eric
E
Nguyen
Université Paris-Sud 11, Orsay, France; Signalisation, Noyaux et Innovations Thérapeutiques en Cancérologie CNRS-UMR 8126, Gustave Roussy, Villejuif, France.
Charles-Henry
CH
Gattolliat
Département de Pédiatrie, Gustave-Roussy, 114 rue Edouard Vaillant, 94805, France.
Dominique
D
Valteau-Couanet
Université Paris-Sud 11, Orsay, France; Signalisation, Noyaux et Innovations Thérapeutiques en Cancérologie CNRS-UMR 8126, Gustave Roussy, Villejuif, France.
Jean
J
Bénard
MAP5, Université Paris Descartes, Sorbonne Paris Cité, France; INSERM UMR-S 1018, 16 bis Avenue Paul Vaillant-Couturier, 94804, Villejuif, France.
Catherine
C
Huber
INSERM UMR-S 1007, Cellular Homeostasis and Cancer, Paris, France; Université Paris-Descartes, Paris Sorbonne Cité, Paris, France. Electronic address: evelyne.segal-bendirdjian@inserm.fr.
Evelyne
E
Ségal-Bendirdjian
D000293:Adolescent; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D018740:Genetic Heterogeneity; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D000071447:N-Myc Proto-Oncogene Protein; D009447:Neuroblastoma / Q000235:genetics* / Q000401:mortality*; D009687:Nuclear Proteins / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D025721:WT1 Proteins / Q000378:metabolism*
D014408:Biomarkers, Tumor; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D025721:WT1 Proteins; C583751:WT1 protein, human
Differentiation; MYCN; Neuroblastoma; Wilms' tumors