scholarly journals Identifying regions of a gene that are susceptible to mutation

2021 ◽  
Vol 87 (01) ◽  
pp. 193-202
Author(s):  
Alper Bulut ◽  
◽  
Fatih Dogan
Keyword(s):  
Weighted Graph ◽  
Tp53 Gene ◽  
Suppressor Gene ◽  
Bond Dissociation Energies ◽  
Energy Distributions ◽  
Short Intervals ◽  
Dissociation Energies ◽  
Gene Tp53 ◽  
Exon 9 ◽  
Exon 4

In this article, the susceptibility of any gene to mutation is explained through the tumor suppressor gene TP53 using the concept of the energy of a graph. We considered the structure of TP53 gene as a weighted graph where the weights are the bond dissociation energies. We computed energies of each exon and investigated how they distributed over the bases. We observed that exons 4 and 12 have unusual energy distributions compared to other exons. The energy was found to be signifi- cantly reduced relative to other regions between the 44th and 47th codons of exon 4, and this is in line with the literature results to which these regions are subject to severe missense and frameshift mutations. The energy of exon 12 changes very rapidly at very short intervals and is not consistently distributed across the exon. The excited energy probability distribution of exon 9 is used to determine the most vulnerable region of exon 9 when subjected to any physical or chemical external influences.

TP53 Mutations in Canine Brain Tumors

2011 ◽  
Vol 49 (5) ◽  
pp. 796-801 ◽  
Author(s):  
D. York ◽  
R. J. Higgins ◽  
R. A. LeCouteur ◽  
A. N. Wolfe ◽  
R. Grahn ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Human Cancer ◽  
Gene Mutations ◽  
Tp53 Gene ◽  
Suppressor Gene ◽  
Cancer Mutation ◽  
Canine Brain ◽  
Gene Tp53 ◽  
Altered Gene ◽  
P53 Inactivation

The p53 tumor suppressor gene ( TP53) is the most frequently altered gene in human cancer. Mutation of the gene has been shown to be an important mechanism of p53 pathway inactivation in a variety of human brain tumors, particularly those of astrocytic origin. Genomic DNA from a series of 37 glial and 51 nonglial canine brain tumors was sequenced to determine the frequency of TP53 gene mutations involving exons 3–9. Exonic mutations were found in 3 of 88 tumors (3.4%) and specifically in 1 of 18 astrocytic tumors (5.5%). This is markedly lower than that reported in comparable human tumors, suggesting that alternative mechanisms of p53 inactivation are likely to be present if p53 function contributes significantly to oncogenesis in canine brain tumors.

scholarly journals The Relationship of Gliomas with Tp53 Rs1042522 C > G And Gliomas in Duhok

2020 ◽  
Vol 23 (2) ◽  
pp. 157-165
Author(s):  
Farida F. A. Nerweyi
Keyword(s):  
Age Groups ◽  
Tp53 Gene ◽  
Suppressor Gene ◽  
Allele Frequencies ◽  
Pcr Analysis ◽  
Healthy Individuals ◽  
Tp53 Arg72pro ◽  
Gene Tp53 ◽  
And Gender ◽  
Tp53 Arg72pro Polymorphism

A tumor suppressor gene TP53 has a central role in controlling the cell cycle, apoptosis, as well as DNA damage repair. A common polymorphism in TP53 is the Arg72Pro exon 4 polymorphism. Polymorphism has been proposed to be associated with genetically determined susceptibility in different types of cancers, including glioma. This study was conducted to estimate the distribution of glioma within age groups, gender, smokers, and residence of individual also to investigate the distribution of TP53 Arg72Pro SNPs genotype in glioma, and determine whether TP53 Arg72Pro polymorphism is a possible relevance in susceptibility to glioma using RFLP-PCR analysis. Enrolled were 65 patients (glioma tissues matched age and gender) and 70 healthy individuals as a control. The findings in glioma samples 40(61.54%) were homozygous for arginine (Arg / Arg), 19 (29.23%) heterozygous for (Arg / Pro), and 6 (9.23%) homozygous for proline (Pro / Pro). Three separate frequencies of genotypes of Arg72Pro; 33 (47.14%), 28 (40.0), and 9 (12.86%) were identified in healthy individuals, respectively. The allele Frequencies for the Pro 72 and Arg 72 gliomas were 16 (24.62%) and 49 (75.38%), respectively. In the Pro 72 and Arg 72 controls, the allele frequencies were 23 (32.86%) and 47 (67.14%), respectively. Finally, there was no significant relationship between age group, gender, dwellers, non-smokers and smokers in different genotypes of codon 72 of TP53 gene (P < 0.05).

scholarly journals The Relationship of Gliomas with Tp53 Rs1042522 C > G And Gliomas in Duhok

2020 ◽  
Vol 23 (2) ◽  
pp. 157-165
Author(s):  
Farida F. A. Nerweyi
Keyword(s):  
Age Groups ◽  
Tp53 Gene ◽  
Suppressor Gene ◽  
Allele Frequencies ◽  
Pcr Analysis ◽  
Healthy Individuals ◽  
Tp53 Arg72pro ◽  
Gene Tp53 ◽  
And Gender ◽  
Tp53 Arg72pro Polymorphism

A tumor suppressor gene TP53 has a central role in controlling the cell cycle, apoptosis, as well as DNA damage repair. A common polymorphism in TP53 is the Arg72Pro exon 4 polymorphism. Polymorphism has been proposed to be associated with genetically determined susceptibility in different types of cancers, including glioma. This study was conducted to estimate the distribution of glioma within age groups, gender, smokers, and residence of individual also to investigate the distribution of TP53 Arg72Pro SNPs genotype in glioma, and determine whether TP53 Arg72Pro polymorphism is a possible relevance in susceptibility to glioma using RFLP-PCR analysis. Enrolled were 65 patients (glioma tissues matched age and gender) and 70 healthy individuals as a control. The findings in glioma samples 40(61.54%) were homozygous for arginine (Arg / Arg), 19 (29.23%) heterozygous for (Arg / Pro), and 6 (9.23%) homozygous for proline (Pro / Pro). Three separate frequencies of genotypes of Arg72Pro; 33 (47.14%), 28 (40.0), and 9 (12.86%) were identified in healthy individuals, respectively. The allele Frequencies for the Pro 72 and Arg 72 gliomas were 16 (24.62%) and 49 (75.38%), respectively. In the Pro 72 and Arg 72 controls, the allele frequencies were 23 (32.86%) and 47 (67.14%), respectively. Finally, there was no significant relationship between age group, gender, dwellers, non-smokers and smokers in different genotypes of codon 72 of TP53 gene (P < 0.05).

scholarly journals Antitumor Effects of PRIMA-1 and PRIMA-1Met (APR246) in Hematological Malignancies: Still a Mutant P53-Dependent Affair?

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 98
Author(s):  
Paola Menichini ◽  
Paola Monti ◽  
Andrea Speciale ◽  
Giovanna Cutrona ◽  
Serena Matis ◽  
...  
Keyword(s):  
Hematological Malignancies ◽  
Cell Metabolism ◽  
Therapy Response ◽  
Tp53 Gene ◽  
Suppressor Gene ◽  
Lower Percentage ◽  
Mutant P53 ◽  
Wild Type ◽  
Antitumor Effects ◽  
Tp53 Tumor Suppressor Gene

Because of its role in the regulation of the cell cycle, DNA damage response, apoptosis, DNA repair, cell migration, autophagy, and cell metabolism, the TP53 tumor suppressor gene is a key player for cellular homeostasis. TP53 gene is mutated in more than 50% of human cancers, although its overall dysfunction may be even more frequent. TP53 mutations are detected in a lower percentage of hematological malignancies compared to solid tumors, but their frequency generally increases with disease progression, generating adverse effects such as resistance to chemotherapy. Due to the crucial role of P53 in therapy response, several molecules have been developed to re-establish the wild-type P53 function to mutant P53. PRIMA-1 and its methylated form PRIMA-1Met (also named APR246) are capable of restoring the wild-type conformation to mutant P53 and inducing apoptosis in cancer cells; however, they also possess mutant P53-independent properties. This review presents the activities of PRIMA-1 and PRIMA-1Met/APR246 and describes their potential use in hematological malignancies.

scholarly journals Experimental bond dissociation energies of benzylpyridinium thermometer ions determined by threshold-CID and RRKM modeling

2017 ◽  
Vol 417 ◽  
pp. 69-75 ◽  
Author(s):  
David Gatineau ◽  
Antony Memboeuf ◽  
Anne Milet ◽  
Richard B. Cole ◽  
Héloïse Dossmann ◽  
...  
Keyword(s):  
Bond Dissociation Energies ◽  
Bond Dissociation ◽  
Dissociation Energies ◽  
Thermometer Ions

scholarly journals Dysfunction of the TP53 tumor suppressor gene in lymphoid malignancies

Blood ◽  
2012 ◽  
Vol 119 (16) ◽  
pp. 3668-3683 ◽  
Author(s):  
Zijun Y. Xu-Monette ◽  
L. Jeffrey Medeiros ◽  
Yong Li ◽  
Robert Z. Orlowski ◽  
Michael Andreeff ◽  
...  
Keyword(s):  
Tp53 Gene ◽  
Suppressor Gene ◽  
Wild Type ◽  
Lymphoid Malignancies ◽  
The Status ◽  
Tp53 Tumor Suppressor Gene ◽  
P53 Activation ◽  
Apoptotic Pathways ◽  
P53 Inactivation ◽  
Tp53 Pathway

AbstractMutations of the TP53 gene and dysregulation of the TP53 pathway are important in the pathogenesis of many human cancers, including lymphomas. Tumor suppression by p53 occurs via both transcription-dependent activities in the nucleus by which p53 regulates transcription of genes involved in cell cycle, DNA repair, apoptosis, signaling, transcription, and metabolism; and transcription-independent activities that induces apoptosis and autophagy in the cytoplasm. In lymphoid malignancies, the frequency of TP53 deletions and mutations is lower than in other types of cancer. Nonetheless, the status of TP53 is an independent prognostic factor in most lymphoma types. Dysfunction of TP53 with wild-type coding sequence can result from deregulated gene expression, stability, and activity of p53. To overcome TP53 pathway inactivation, therapeutic delivery of wild-type p53, activation of mutant p53, inhibition of MDM2-mediated degradation of p53, and activation of p53-dependent and -independent apoptotic pathways have been explored experimentally and in clinical trials. We review the mechanisms of TP53 dysfunction, recent advances implicated in lymphomagenesis, and therapeutic approaches to overcoming p53 inactivation.

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