Nucleotide variations of TP53 exon 4 found in intracranial meningioma and in silico prediction of their significance.

ABSTRACT

The aim of the present study was to identify TP53 exon 4 mutations in patients with meningioma and to investigate their potential association with specific tumor pathology. Nucleotide alterations were investigated in 48 meningiomas via the direct sequencing of TP53 exon 4 in patient tumor and blood samples using the DNA Sanger method with the BigDyeTerminator v3.1 Cycle Sequencing kit and Applied Biosystems 3730XL apparatus. The results revealed that TP53 exon 4 was frequently altered in meningioma, occurring in 60.4% of the patients investigated. A total of 18 different alterations were detected in the meningioma samples assessed in the current study. The majority of these appeared more than once and some were repeatedly identified in several patients. Changes at codons 72 (c.215G>C) and 62 (c.186delA) were highly prevalent, occurring in 44.8% of patients. Other changes detected via frequency analysis included Five substitutions on codon 105 (c.315C>T); four insertions on codon 70 (c.209_210insG); three insertions on codon 64 (c.190C>G), 82 (245C>T; 245delC; 243_244insA) and 104 (c.312G>A); and two insertions on codons 108 (c.322G>C), 71 (c.213C>A), 73 (c.217G>A), 91 (c.271T>C) and 100 (c.300G>T). Codons 68 (c.202_203insT), 77 (c.229C>T), 88 (c.263C>G) and 92 (c.276C>A) were altered once. Alterations on codons 82, 91, 108, 104, 105, 70 and 92 were characterized as possibly damaging by PolyPhen-2 and Mutation Taster2 tools. The current study also demonstrated that nucleotide alterations were significantly associated with the loss of p53 expression (P=0.04) and female patients (P=0.049), particularly codon 72. The results present novel data on the mutational spectrum of TP53 in meningeal brain tumors.