Polμ deficiency induces moderate shortening of P53−/− mouse lifespan and modifies tumor spectrum

Escudero, Beatriz; Herrero, Diego; Torres, Yaima; Cañón, Susana; Molina, Antonio; Carmona, Rosa María; Suela, Javier; Blanco, Luis; Samper, Enrique; Bernad, António

doi:10.1016/j.dnarep.2017.04.001

Cited by 2 publications

(3 citation statements)

References 45 publications

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“…The overexpression of lig4 found in our population cannot be associated with LOH, though it is important evidence of NHEJ deregulation. Deletion of polμ has been shown to be associated with sarcoma development in p53-/-mice (25). Our data highlight the importance of POLμ downregulation in ES tumor samples.…”

Section: Discussionsupporting

confidence: 59%

Expression of DNA Repair Genes in Ewing Sarcoma

KYRIAZOGLOU,

MOUTAFI,

ZOGRAFOS

et al. 2024

CDP

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Background/Aim: Ewing sarcoma is an aggressive mesenchymal malignancy commonly affecting children and young adolescents. The molecular basis of this neoplasia is well reported with the formation of the EWSR1/FLI1 fusion gene being the most common genetic finding. However, this fusion gene has not been targeted therapeutically nor is being used as a prognostic marker. Its relevance regarding the molecular steps leading to Ewing sarcoma genesis are yet to be defined. The generation of the oncogenic EWSR1/FLI1 fusion gene, can be attributed to the simultaneous introduction of two DNA double-strand breaks (DSBs). The scope of this study is to detect any association between DNA repair deficiency and the clinicopathological aspects of Ewing’s sarcoma disease. Patients and Methods: We have conducted an expression analysis of 35 patients diagnosed with Ewing sarcoma concerning the genes involved in non-homologous end joining (NHEJ) and homologous recombination (HR) repair pathways. We have analyzed the expression levels of 6 genes involved in NHEJ (XRCC4, XRCC5, XRCC6, POLλ, POLμ) and 9 genes involved in HR (RAD51, RAD52, RAD54, BRCA1, BRCA2, FANCC, FANCD, DNTM1, BRIT1) using real time PCR. Age, sex, location of primary tumor, tumor size, KI67, mitotic count, invasion of adjacent tissues and treatment were the clinicopathological parameters included in the statistical analysis. Results: Our results show that both these DNA repair pathways are deregulated in Ewing sarcoma. In addition, low expression of the xrcc4 gene has been associated with better overall survival probability (p=0.032). Conclusion: Our results, even though retrospective and in a small number of patients, highlight the importance of DSBs repair and propose a potential therapeutic target for this type of sarcoma.

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Section: Discussionsupporting

confidence: 59%

Expression of DNA Repair Genes in Ewing Sarcoma

KYRIAZOGLOU,

MOUTAFI,

ZOGRAFOS

et al. 2024

CDP

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“…We identified another gene, Polm , which was overexpressed following perinatal exposure to HMB relative to control rats. Polm is a member of the X family of DNA polymerases whose primary function is to prevent tumorigenesis by a repair of DNA damages [57,58]. Previous studies have reported that polm may also act to repair DNA damage in the prostate [58].…”

Section: Discussionmentioning

confidence: 99%

“…Polm is a member of the X family of DNA polymerases whose primary function is to prevent tumorigenesis by a repair of DNA damages [57,58]. Previous studies have reported that polm may also act to repair DNA damage in the prostate [58]. Similar to the genes discussed above, Polm ’s function in the prostatehas not been well understood.…”

Section: Discussionmentioning

confidence: 99%

Transcript profiling in the testes and prostates of postnatal day 30 Sprague-Dawley rats exposed prenatally and lactationally to 2-hydroxy-4-methoxybenzophenone

Nakamura

Vijay

Desai

et al. 2018

Reproductive Toxicology

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2-hydroxy-4-methoxybenzophenone (HMB) is an ultraviolet (UV) light-absorbing compound that is used in sunscreens, cosmetics and plastics. HMB has been reported to have weak estrogenic activity by in vivo and in vitro studies, making it a chemical with potential reproductive concern. To explore if perinatal HMB exposure altered the gene expression profiling in the rat prostate and testis, we performed microarray gene expression profiling on the prostate and testis from Sprague-Dawley rat offspring fed various doses of HMB (0, 3000, or 30000 ppm) in 5K96 low phytoestrogen chow from gestational day (GD) 6 through postnatal day (PND) 21. Gene expression profiles of the prostate and testis were differentially affected by HMB dose and duration of exposure, and also indicated tissue-specific alterations. These genes that altered expression indicate a potential utility of candidate biomarker(s) for testicular or prostatic toxicity. Further studies are necessary to explore this potential.

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Polμ deficiency induces moderate shortening of P53−/− mouse lifespan and modifies tumor spectrum

Cited by 2 publications

References 45 publications

Expression of DNA Repair Genes in Ewing Sarcoma

Expression of DNA Repair Genes in Ewing Sarcoma

Transcript profiling in the testes and prostates of postnatal day 30 Sprague-Dawley rats exposed prenatally and lactationally to 2-hydroxy-4-methoxybenzophenone

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