Association between TP53 gene ARG72PRO polymorphism and chromosome aberrations in human cancers

Litviakov, N. V.; Denisov, Evgeny V.; Takhauov, R. M.; Karpov, A.B.; Skobel'skaja, Elena V.; Васильева, Е. О.; Гончарик, О О; Агеева, А. М.; Mamonova, Natalya V.; Mezheritskiy, Stanislav A.; Sevost'janova, Natalya V.; Кошель, А. П.

doi:10.1002/mc.20633

Cited by 14 publications

(5 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Siddique & Sabapathy 21 reported that Pro-expressing cells exhibit reduced micronuclei formation compared to Arg-expressing cells. Later, Litviakov 33 showed that cancer patients with Pro/Pro genotype have fewer chromatid breaks in comparison to Arg/Pro and Arg/Arg carriers. Moreover, chromosomal radiosensitivity, as measured by the G2-chromosome break assay, has been reported to be associated with polymorphisms in TP53 codon 72 34 .…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in MDM2 and TP53 Genes and Risk of Developing Therapy-Related Myeloid Neoplasms

Cabezas

Garcia-Quevedo

Alonso

et al. 2019

Sci Rep

View full text Add to dashboard Cite

One of the most severe complications after successful cancer therapy is the development of therapy-related myeloid neoplasms (t-MN). Constitutional genetic variation is likely to impact on t-MN risk. We aimed to evaluate if polymorphisms in the p53 pathway can be useful for predicting t-MN susceptibility. First, an association study revealed that the Pro variant of the TP53 Arg72Pro polymorphism and the G allele of the MDM2 SNP309 were associated with t-MN risk. The Arg variant of TP53 is more efficient at inducing apoptosis, whereas the Pro variant is a more potent inductor of cell cycle arrest and DNA repair. As regards MDM2 SNP309, the G allele is associated with attenuation of the p53 apoptotic response. Second, to evaluate the biological effect of the TP53 polymorphism, we established Jurkat isogenic cell lines expressing p53Arg or p53Pro. Jurkat p53Arg cells presented higher DNA damage and higher apoptotic potential than p53Pro cells, after treatment with chemotherapy agents. Only p53Pro cells presented t(15;17) translocation and del(5q). We suggest that failure to repair DNA lesions in p53Arg cells would lead them to apoptosis, whereas some p53Pro cells, prone to cell cycle arrest and DNA repair, could undergo misrepair, generating chromosomal abnormalities typical of t-MN.

show abstract

Section: Discussionmentioning

confidence: 99%

Polymorphisms in MDM2 and TP53 Genes and Risk of Developing Therapy-Related Myeloid Neoplasms

Cabezas

Garcia-Quevedo

Alonso

et al. 2019

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The variant Pro allele has been shown to be less efficient in suppressing cell transformation and inducing apoptosis and to be less sensitive to degradation by viral oncogenic proteins (11). However, other recent reports have pointed out that the Arg variant is a less efficient DNA repair molecule and therefore Arg/Arg carriers may have an increased frequency of chromosomal aberrations and a high level of genomic instability (34,35). …”

Section: Discussionmentioning

confidence: 99%

Role of p53 codon 72 polymorphism in chromosomal aberrations and mitotic index in patients with chronic hepatitis B

Akbas

Yalçın

Isi

et al. 2012

Braz J Med Biol Res

View full text Add to dashboard Cite

Polymorphisms of the p53 gene, which participates in DNA repair, can affect the functioning of the p53 protein. The Arg and Pro variants in p53 codon 72 were shown to have different regulation properties of p53-dependent DNA repair target genes that can affect various levels of cytogenetic aberrations in chronic hepatitis B patients. The present study aimed to examine the frequency of chromosomal aberrations and the mitotic index in patients with chronic hepatitis B and their possible association with p53 gene exon 4 codon 72 Arg72Pro (Ex4+119 G>C; rs1042522) polymorphism. Fifty-eight patients with chronic hepatitis B and 30 healthy individuals were genotyped in terms of the p53 gene codon 72 Arg72Pro polymorphism by PCR-RFLP. A 72-h cell culture was performed on the same individuals and evaluated in terms of chromosomal aberrations and mitotic index. A high frequency of chromosomal aberrations and low mitotic index were detected in the patient group compared to the control group. A higher frequency of chromosomal aberrations was detected in both the patient and the control groups with a homozygous proline genotype (13 patients, 3 control subjects) compared to patients and controls with other genotypes [Arg/Pro (38 patients, 20 control subjects) and Arg/Arg (7 patients, 7 control subjects)]. We observed an increased frequency of cytogenetic aberrations in patients with chronic hepatitis B. In addition, a higher frequency of cytogenetic aberrations was observed in p53 variants having the homozygous proline genotype compared to variants having other genotypes both in patients and healthy individuals.

show abstract

“…For example, the TP53 tumor suppressor gene is mutated in >50% of human tumors [42]. Among the 393 amino acids of P53, sequences at positions 5-28 have p53 transcription activity and pathogenic mutations are enriched at R248Q, R273H, and R282W which affect DNA binding, or in R175H, Y220C, G245S, and R249S which are called conformational mutations [43,44]. The mechanism of p53 in cancer development has been thoroughly investigated, with more than 70K papers published since 1979.…”

Section: Loss Of Heterozygosity Provides Novel Therapeutic Targets For Cancer Treatmentmentioning

confidence: 99%

Targeting Loss of Heterozygosity: A Novel Paradigm for Cancer Therapy

Zhang

Sjöblom

2021

Pharmaceuticals

View full text Add to dashboard Cite

Loss of heterozygosity (LOH) is a common genetic event in the development of cancer. In certain tumor types, LOH can affect more than 20% of the genome, entailing loss of allelic variation in thousands of genes. This reduction of heterozygosity creates genetic differences between tumor and normal cells, providing opportunities for development of novel cancer therapies. Here, we review and summarize (1) mutations associated with LOH on chromosomes which have been shown to be promising biomarkers of cancer risk or the prediction of clinical outcomes in certain types of tumors; (2) loci undergoing LOH that can be targeted for development of novel anticancer drugs as well as (3) LOH in tumors provides up-and-coming possibilities to understand the underlying mechanisms of cancer evolution and to discover novel cancer vulnerabilities which are worth a further investigation in the near future.

show abstract

Association between TP53 gene ARG72PRO polymorphism and chromosome aberrations in human cancers

Cited by 14 publications

References 16 publications

Polymorphisms in MDM2 and TP53 Genes and Risk of Developing Therapy-Related Myeloid Neoplasms

Polymorphisms in MDM2 and TP53 Genes and Risk of Developing Therapy-Related Myeloid Neoplasms

Role of p53 codon 72 polymorphism in chromosomal aberrations and mitotic index in patients with chronic hepatitis B

Targeting Loss of Heterozygosity: A Novel Paradigm for Cancer Therapy

Contact Info

Product

Resources

About