TP53 codon 72 polymorphism may predict early tumour progression in paediatric pilocytic astrocytoma
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Samantha Mascelli1, Paolo Nozza2, David T.W. Jones3, Carole Colin4, Angela Pistorio5, Claudia Milanaccio1, Marcello Ravegnani1, Alessandro Consales1, Olaf Witt6, Giovanni Morana7, Armando Cama1, Valeria Capra1, Roberto Biassoni8, Stefan M. Pfister3,6, Dominique Figarella-Branger4,9, Maria Luisa Garrè10, Alessandro Raso1
1Dipartimento Testa, Collo e Neuroscienze, Istituto Giannina Gaslini, 16147 Genoa, Italy
2UOC Anatomia Patologica, Istituto Giannina Gaslini, 16147 Genoa, Italy
3Division of Paediatric Neurooncology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany
4CRO2 UMR_S911, Inserm, Aix-Marseille Université, 13385 Marseille, France
5Epidemiologia, Biostatistica e Comitati, Istituto Giannina Gaslini, 16147 Genoa, Italy
6Department of Paediatric Oncology, Haematology and Immunology, University of Heidelberg, Heidelberg, 69120 Heidelberg, Germany
7Neuroradiologia Istituto Giannina Gaslini, 16147 Genoa, Italy
8Laboratory Molecular Medicine, Translational Medicine Department, Istituto Giannina Gaslini, 16147 Genoa, Italy
9APHM, Hôpital de la Timone, Service d’Anatomie Pathologique et de Neuropathologie, 13385 Marseille, France
10Centro di Neuro-Oncologia, Istituto Giannina Gaslini, 16147 Genoa, Italy
Samantha Mascelli, email: [email protected]
Keywords: low-grade gliomas, polymorphism, pilocytic astrocytoma, paediatric, TP53
Received: March 25, 2016 Accepted: May 10, 2016 Published: June 25, 2016
Pilocytic astrocytoma and ganglioglioma may occur in inaccessible or surgically difficult areas. In case of incomplete resection, the availability of biological predictors of tumour progression could be particularly important. To this end, an analysis of p53 codon 72 polymorphism and assessment of its role as prognostic marker were performed.
The status of the p53 Arg72Pro polymorphism was evaluated by pyrosequencing method in a multicenter cohort of 170 paediatric patients. Genotype/phenotype associations were investigated either by means of bivariate or multivariate analyses.
In the partially resected pilocytic astrocytomas, the Arg/Arg variant predicts early tumour progression (median survival time: 23.1 months) and is associated with poor event-free survival (p value = 0.0009). This finding remains true also in case of adjuvant therapies, with a 5-year event-free survival of 30.6% for cases with Arg/Arg variant vs. 78.7% for those with other genotypes. There is no association between ganglioglioma and the polymorphism.
The assessment of Arg/Arg variant could improve the management of pilocytic astrocytoma. TP53 codon 72 analysis could distinguish low-risk cases, in which surgery could be conservative, from high-risk cases needing an aggressive surgery plan.
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