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Journal of Neurosurgical Sciences 2018 Jan 04
DOI: 10.23736/S0390-5616.18.04284-4
Copyright © 2018 EDIZIONI MINERVA MEDICA
lingua: Inglese
Blood-tissue analysis of TP53 polymorphisms and survival of patients with glioma
Pier P. PANCIANI 1 ✉, Maria T. GIORDANA 2, Salvatore GALLONE 3, Andrea MURATORI 4, Rosaria ROTUNNO 5, Karol MIGLIORATI 4, Giannantonio SPENA 1, Alessandro DUCATI 6, Marco FONTANELLA 4
1 U.O. di Neurochirurgia, ASST Spedali Civili di Brescia, Brescia, Italy; 2 Clinica Neurologica, Dipartimento di Neuroscienze, Università degli Studi di Torino, Torino, Italy; 3 U.O. di Neurogenetica Clinica, Dipartimento di Neuroscienze, Università degli Studi di Torino, Torino, Italy; 4 U.O. di Neurochirurgia, Dipartimento di Specialità Medico-Chirurgiche, Scienze Radiologiche e Sanità Pubblica, Università degli Studi di Brescia, Brescia, Italy; 5 U.O. Di Neurochirurgia, Fondazione Poliambulanza di Brescia, Brescia, Italy; 6 U.O. di Neurochirurgia, Dipartimento di Neuroscienze, Università degli Studi di Torino, Torino, Italy
BACKGROUND: The role of single nucleotide polymorphisms (SNPs) in TP53 in the pathogenesis of glioma is debated. The aim of our study was to investigate the role of several TP53 SNPs in the risk of glioma and their possible role as prognostic biomarkers of overall and progression-free survival.
METHODS: We examined 12 SNPs in TP53 from peripheral blood and neoplastic tissue of patients with a diagnosis of glioma who underwent surgery from 2012 to 2015. Direct genomic sequencing of TP53 was performed to detect the presence of polymorphisms. We compared data with a matched cancer-free control group and the NCBI SNPs database. Overall and progression-free survival were analyzed in patients with glioblastoma subjected to gross total resection and concomitant radio- chemotherapy.
RESULTS: No association was observed with glioma susceptibility and overall survival. Two new SNPs were detected: c.97-46 G>A (intron 3) and c.783-31 A>G (intron 7). The number of SNPs observed was higher (21.4%) in blood than in tumoral samples. We observed a significant reduction in progression-free survival in patients with at least one exonic SNP.
CONCLUSIONS: We can hypothesize an involvement of TP53 SNPs in response mechanisms to adjuvant treatment that may affect progression-free survival. Moreover, our blood-tissue combined study revealed a significant difference in SNPs between blood and tumoral samples, probably due to glioma heterogeneity and genomic instability.
KEY WORDS: TP53 - Polymorphism - Glioma - Susceptibility - Survival