Functional deficiency of DNA repair gene EXO5 results in androgen-induced genomic instability and prostate tumorigenesis

Genomic instability has been an area of active area of research in the last two decades. Based on the initial study for hereditary cancers, DNA repair gene family mutations have been identified. In sporadic (non-hereditary) cancers, several large-scale DNA sequencing studies suggest that mutations in DNA repair genes are less frequent, suggesting the complexity of tumorigenesis of sporadic cancers. So far, several important genes have been identified, by using mostly cell line models and mice studies. These include DNA damage response modifier like ataxia telangiectasia mutated (ATM), conventional tumor suppressor genes like TP53 and cyclin-dependent kinase inhibitor 2A (CDKN2A; which encodes p16INK4A and p14ARF). Various hypotheses for sporadic tumorigenesis have been developed, and so far, “oncogene-induced DNA replication stress model” has been gaining widespread interests. In this review, we will first describe some of the important concepts of genomic instability. Then, we will outline oncogene-induced genomic instability and discuss the role of the MYC gene during this process, which will be followed by detailed reviews of mutation data. We hope that this review can outline the overall perspectives of genomic instability. Impact statement This review provides various genetic and cell line data previously published in a way to explain how cellular stress can lead into genetic instability.

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Female age affects DNA repair gene expression in mouse GV oocytes from stimulated and unstimulated cycles and in MII oocytes matured in-vivo and in-vitro

10.26226/morressier.5af300ae738ab10027aa9430 ◽

2018 ◽

Author(s):

AR AR ◽

Sally Catt

Keyword(s):

Gene Expression ◽

Dna Repair ◽

Repair Gene ◽

Female Age ◽

Dna Repair Gene ◽

Mouse Gv Oocytes

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Faculty Opinions recommendation of Intraductal/ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.732569033.793548738 ◽

2018 ◽

Author(s):

Valeri Vasioukhin

Keyword(s):

Prostate Cancer ◽

Dna Repair ◽

Lymphovascular Invasion ◽

Gene Mutations ◽

Repair Gene ◽

Dna Repair Gene

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DNA Repair Gene Polymorphism and the Risk of Mitral Chordae Tendineae Rupture

Disease Markers ◽

10.1155/2015/825020 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6

Author(s):

Aysel Kalayci Yigin ◽

Mehmet Bulent Vatan ◽

Ramazan Akdemir ◽

Muhammed Necati Murat Aksoy ◽

Mehmet Akif Cakar ◽

...

Keyword(s):

Dna Repair ◽

Fragment Length Polymorphism ◽

Control Group ◽

Chordae Tendineae ◽

Repair Gene ◽

Repair Capacity ◽

Dna Repair Capacity ◽

Dna Repair Gene ◽

Increased Risk ◽

Polymerase Chain

Polymorphisms in Lys939Gln XPC gene may diminish DNA repair capacity, eventually increasing the risk of carcinogenesis. The aim of the present study was to evaluate the significance of polymorphism Lys939Gln in XPC gene in patients with mitral chordae tendinea rupture (MCTR). Twenty-one patients with MCTR and thirty-seven age and sex matched controls were enrolled in the study. Genotyping of XPC gene Lys939Gln polymorphism was carried out using polymerase chain reaction- (PCR-) restriction fragment length polymorphism (RFLP). The frequencies of the heterozygote genotype (Lys/Gln-AC) and homozygote genotype (Gln/Gln-CC) were significantly different in MCTR as compared to control group, respectively (52.4% versus 43.2%,p=0.049; 38.15% versus 16.2%,p=0.018). Homozygote variant (Gln/Gln) genotype was significantly associated with increased risk of MCTR (OR = 2.059; 95% CI: 1.097–3.863;p=0.018). Heterozygote variant (Lys/Gln) genotype was also highly significantly associated with increased risk of MCTR (OR = 1.489; 95% CI: 1.041–2.129;p=0.049). The variant allele C was found to be significantly associated with MCTR (OR = 1.481; 95% CI: 1.101–1.992;p=0.011). This study has demonstrated the association of XPC gene Lys939Gln polymorphism with MCTR, which is significantly associated with increased risk of MCTR.

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DNA Repair Gene Polymorphisms and Susceptibility to Urothelial Carcinoma in a Southeastern European Population

Current Oncology ◽

10.3390/curroncol28030174 ◽

2021 ◽

Vol 28 (3) ◽

pp. 1879-1885

Author(s):

Maria Samara ◽

Maria Papathanassiou ◽

Lampros Mitrakas ◽

George Koukoulis ◽

Panagiotis J. Vlachostergios ◽

...

Keyword(s):

Dna Repair ◽

Urothelial Carcinoma ◽

European Population ◽

Nucleotide Polymorphisms ◽

Environmental Carcinogens ◽

Repair Gene ◽

High Exposure ◽

Dna Repair Gene ◽

Increased Risk ◽

Xrcc3 Thr241met

Single nucleotide polymorphisms (SNPs) in DNA repair genes may predispose to urothelial carcinoma of the bladder (UCB). This study focused on three specific SNPs in a population with high exposure to environmental carcinogens including tobacco and alcohol. A case-control study design was used to assess for presence of XPC PAT +/−, XRCC3 Thr241Met, and ERCC2 Lys751Gln DNA repair gene SNPs in peripheral blood from patients with UCB and healthy individuals. One hundred patients and equal number of healthy subjects were enrolled. The XPC PAT +/+ genotype was associated with a 2-fold increased risk of UCB (OR = 2.16; 95%CI: 1.14–4; p = 0.01). The −/+ and +/+ XPC PAT genotypes were more frequently present in patients with multiple versus single tumors (p = 0.01). No association was detected between ERCC2 Lys751Gln genotypes/alleles, and risk for developing UCB. Presence of the XRCC3 TT genotype (OR = 0.14; 95%CI:0.07–0.25; p < 0.01) and of the T allele overall (OR = 0.26; 95%CI:0.16–0.41; p < 0.01) conferred a protective effect against developing UCB. The XPC PAT −/+ and XRCC3 Thr241Met SNPs are associated with predisposition to UCB. The XPC PAT −/+ SNP is also an indicator of bladder tumor multiplicity, which might require a more individualized surveillance and treatment.

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Patients with Systemic Sclerosis Present Increased DNA Damage Differentially Associated with DNA Repair Gene Polymorphisms

The Journal of Rheumatology ◽

10.3899/jrheum.130376 ◽

2014 ◽

Vol 41 (3) ◽

pp. 458-465 ◽

Cited By ~ 11

Author(s):

Gustavo Martelli Palomino ◽

Carmen L. Bassi ◽

Isabela J. Wastowski ◽

Danilo J. Xavier ◽

Yara M. Lucisano-Valim ◽

...

Keyword(s):

Dna Damage ◽

Dna Repair ◽

Systemic Sclerosis ◽

Blood Cells ◽

Gene Polymorphisms ◽

Peripheral Blood Cells ◽

Dna Repair Genes ◽

Repair Gene ◽

Dna Repair Gene ◽

Repair Genes

Objective.Patients with systemic sclerosis (SSc) exhibit increased toxicity when exposed to genotoxic agents. In our study, we evaluated DNA damage and polymorphic sites in 2 DNA repair genes (XRCC1Arg399Gln andXRCC4Ile401Thr) in patients with SSc.Methods.A total of 177 patients were studied for DNA repair gene polymorphisms. Fifty-six of them were also evaluated for DNA damage in peripheral blood cells using the comet assay.Results.Compared to controls, the patients as a whole or stratified into major clinical variants (limited or diffuse skin involvement), irrespective of the underlying treatment schedule, exhibited increased DNA damage.XRCC1(rs: 25487) andXRCC4(rs: 28360135) allele and genotype frequencies observed in patients with SSc were not significantly different from those observed in controls; however, theXRCC1Arg399Gln allele was associated with increased DNA damage only in healthy controls and theXRCC4Ile401Thr allele was associated with increased DNA damage in both patients and controls. Further, theXRCC1Arg399Gln allele was associated with the presence of antinuclear antibody and anticentromere antibody. No association was observed between these DNA repair gene polymorphic sites and clinical features of patients with SSc.Conclusion.These results corroborate the presence of genomic instability in SSc peripheral blood cells, as evaluated by increased DNA damage, and show that polymorphic sites of theXRCC1andXRCC4DNA repair genes may differentially influence DNA damage and the development of autoantibodies.

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