<i><scp>TP53</scp></i> mutations in astrocytic gliomas: an association with histological grade, <i><scp>TP53</scp></i> codon 72 polymorphism and p53 expression

Faria, M.; Filho, Eduardo Henrique Cunha Neves; Alves, Markênia Kélia Santos; Burbano, Rommel Rodrı́guez; Filho, Manoel Odorico de Moraes; Rabenhorst, Sílvia Helena Barem

doi:10.1111/j.1600-0463.2012.02918.x

Cited by 9 publications

(6 citation statements)

References 21 publications

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“…The described Arg72Pro amino acid change at codon 72 (rs1042522) is a well‐known single nucleotide polymorphism, which frequently occurs in various tumour sites including brain tumours such as glioblastoma (Faria et al . ). Codon 72 in exon 4 is coding for the polyproline domain, in which many tumour‐associated mutations are observed.…”

Section: Discussionmentioning

confidence: 97%

Loss of p53 expression is accompanied by upregulation of beta‐catenin in meningiomas: a concomitant reciprocal expression

Pećina‐Šlaus

Kafka

Vladušić

et al. 2016

Int J Experimental Path

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Crosstalk between Wnt and p53 signalling pathways in cancer has long been suggested. Therefore in this study we have investigated the involvement of these pathways in meningiomas by analysing their main effector molecules, beta-catenin and p53. Cellular expression of p53 and beta-catenin proteins and genetic changes in TP53 were analysed by immunohistochemistry, PCR/RFLP and direct sequencing of TP53 exon 4. All the findings were analysed statistically. Our analysis showed that 47.5% of the 59 meningiomas demonstrated loss of expression of p53 protein. Moderate and strong p53 expression in the nuclei was observed in 8.5% and 6.8% of meningiomas respectively. Gross deletion of TP53 gene was observed in one meningioma, but nucleotide alterations were observed in 35.7% of meningiomas. In contrast, beta-catenin, the main Wnt signalling molecule, was upregulated in 71.2%, while strong expression was observed in 28.8% of meningiomas. The concomitant expressions of p53 and beta-catenin were investigated in the same patients. In the analysed meningiomas, the levels of the two proteins were significantly negatively correlated (P = 0.002). This indicates that meningiomas with lost p53 upregulate beta-catenin and activate Wnt signalling. Besides showing the reciprocal relationship between proteins, we also showed that the expression of p53 was significantly (P = 0.021) associated with higher meningioma grades (II and III), while beta-catenin upregulation was not associated with malignancy grades. Additionally, women exhibited significantly higher values of p53 loss when compared to males (P = 0.005). Our findings provide novel information about p53 involvement in meningeal brain tumours and reveal the complex relationship between Wnt and p53 signalling, they suggest an important role for beta-catenin in these tumours.

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Section: Discussionmentioning

confidence: 97%

Loss of p53 expression is accompanied by upregulation of beta‐catenin in meningiomas: a concomitant reciprocal expression

Pećina‐Šlaus

Kafka

Vladušić

et al. 2016

Int J Experimental Path

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“…Exon 1 is non-coding in the human p53 protein and for this reason was not analyzed in this study. Exons 2–11 of the TP53 gene were separately amplified by PCR using the specific primer sets described in Faria et al [ 18 ] The direct sequencing analysis of the amplified products was performed using the automatic sequencer ABI Prism 3130 (Thermo Fisher Scientific, USA). The resulting sequences were directly edited on the Sequencing Analysis Software on a computer linked to a 3730XL DNA Analyzer (Thermo Fisher Scientific, USA).…”

Section: Methodsmentioning

confidence: 99%

HPV positive, wild type TP53, and p16 overexpression correlate with the absence of residual tumors after chemoradiotherapy in anal squamous cell carcinoma

et al. 2018

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BackgroundAnal residual tumors are consensually identified within six months of chemoradiotherapy and represent a persistent lesion that may have prognostic value for overall survival. The aim of this study was to evaluate the association of HPV and HIV status, p16 expression level and TP53 mutations with the absence of residual tumors (local response) in Squamous Cell Carcinoma (SCC) of the anal canal after chemoradiotherapy.MethodsWe performed a study on 78 patients with SCC of the anal canal who submitted to chemoradiotherapy and were followed for a six-month period to identify the absence or presence of residual tumors. HPV DNA was identified by polymerase chain reaction and direct sequencing, HIV RNA was detected by TaqMan amplification, p16 expression was detected by western blotting, and the mutational analysis of TP53 was performed by direct sequencing; additionally, samples carrying mutations underwent fluorescent in sit hybridization. The evaluation of the tumor response to treatment was conducted six months after the conclusion of chemoradiotherapy. The following classifications were used to evaluate the outcomes: a) no response (presence of residual tumor) and b) complete response (absence of residual tumor).ResultsThe significant variables associated with the absence of residual tumors were HPV positive, p16 overexpressed, wild-type TP53, female gender, and stages I and II. Only the presence of HPV was independently correlated with the clinical response; this variable increased the chances of a response within six months by 31-fold.ConclusionsThe presence of HPV in tumor cells was correlated with the absence of a residual tumor. This correlation is valuable and can direct future therapeutic approaches in the anal canal.

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“…A total of 32.5% of meningioma investigated by our study showed nucleotide alterations in codons 72 and 62 (each making 44.8% of total mutations found) when compared to blood DNA and database sequences (IARC T53 Database ; p53 Knowledge base ), making these changes highly represented in meningioma. The codon 72 is a known single nucleotide polymorphism reviewed by expert panel and validated, which results in Arg72Pro amino acid change (c.215G>C; p.R72P; rs1042522) and frequently differs in tumors (43). The codon is coding within the polyproline domain of p53 protein well known for harboring many tumor-associated mutations.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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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.

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TP53 mutations in astrocytic gliomas: an association with histological grade, TP53 codon 72 polymorphism and p53 expression

Cited by 9 publications

References 21 publications

Loss of p53 expression is accompanied by upregulation of beta‐catenin in meningiomas: a concomitant reciprocal expression

Loss of p53 expression is accompanied by upregulation of beta‐catenin in meningiomas: a concomitant reciprocal expression

HPV positive, wild type TP53, and p16 overexpression correlate with the absence of residual tumors after chemoradiotherapy in anal squamous cell carcinoma

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

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