Expression of DeltaNp73 is a molecular marker for adverse outcome in neuroblastoma patients.
The p73 gene is a p53 homologue which induces apoptosis and inhibits cell proliferation. Although p73 maps at 1p36.3 and is frequently deleted in neuroblastoma (NB), it does not act as a classic oncosuppressor gene. In developing sympathetic neurons of mice, p73 is predominantly expressed as a truncated anti-apoptotic isoform (DeltaNp73), which antagonizes both p53 and the full-length p73 protein (TAp73). This suggests that p73 may be part of a complex tumor-control mechanism. To determine the role of DeltaNp73 in NB we analyzed the pattern of expression of this gene in vivo and evaluated the prognostic significance of its expression. Our results indicate that DeltaNp73 expression is associated with reduced apoptosis in a NB tumor tissue. Expression of this variant in NB patients significantly correlates with age at diagnosis and VMA urinary excretion. Moreover it is strongly associated with reduced survival (HR=7.93; P<0.001) and progression-free survival (HR=5.3; P<0.001) and its role in predicting a poorer outcome is independent from age, primary tumor site, stage and MYCN amplification (OS: HR=5.24, P=0.012; PFS: HR=4.36, P=0.005). In conclusion our data seem to indicate that DeltaNp73 is a crucial gene in neuroblastoma pathogenesis.
Casciano
I
I
Laboratory of Population Genetics, Istituto Nazionale per la Ricerca sul Cancro (IST), Largo Rosanna Benzi 10, 16132 Genova, Italy.
Mazzocco
K
K
Boni
L
L
Pagnan
G
G
Banelli
B
B
Allemanni
G
G
Ponzoni
M
M
Tonini
G P
GP
Romani
M
M
D017209:Apoptosis / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D016147:Genes, Tumor Suppressor; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009447:Neuroblastoma / Q000175:diagnosis* / Q000401:mortality; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D011379:Prognosis; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D015996:Survival Rate; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human