Is there a role for PCR-SSCP among the methods for missense mutation detection of TP53 gene?

Peltonen, Jenni; Welsh, Judith A.; Vähäkangas, Kirsi

doi:10.1177/0960327107071918

Cited by 4 publications

(2 citation statements)

References 106 publications

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“…Therefore, the mutations in the P53 gene have a great impact on cancer development and maybe a clinically useful predictor of prognosis in mammals (Nakamori et al, 1995). The analysis by single-strand conformation polymorphism (SSCP) method allows the detection of different types of mutations such as base substitutions, small insertions, deletions, and rearrangements (Peltonen, Welsh, and Vahakangas 2007).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of The Mutagenicity and Oxidative Stress of Fipronil After Subchronic Exposure in Male Albino Rats

Noaishi

Eweis

Saleh

et al. 2021

Egyptian Academic Journal of Biological Sciences, F. Toxicology

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Fipronil (FPN) is a pesticide that belongs to the phenylpyrazole chemical group. It is an insecticide with widespread use in the control of many agricultural and domestic pests (Badgujar et al., 2017). The usage of FPN has increased considerably as it is replacing conventional pesticides, such as organophosphates, carbamates, and pyrethroids insecticides, which become less effective against resistant pest strains (Narahashi et al., 2010).

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Section: Discussionmentioning

confidence: 99%

Evaluation of The Mutagenicity and Oxidative Stress of Fipronil After Subchronic Exposure in Male Albino Rats

Noaishi

Eweis

Saleh

et al. 2021

Egyptian Academic Journal of Biological Sciences, F. Toxicology

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“…Two different temperatures (4°C and 20°C) were used to obtain good efficiency. Several studies have shown that the optimization of SSCP conditions is essential for analytical sensitivity and efficiency (for review see) [26]. Both negative and positive controls were included in each run to ensure the quality of the run.…”

Section: Methodsmentioning

confidence: 99%

Specific TP53 mutations predict aggressive phenotype in head and neck squamous cell carcinoma: a retrospective archival study

et al. 2011

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BackgroundHead and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy in the world in developed countries. Despite the intense research in the area of squamous cell carcinomas of head and neck (HNSCC), long-term survival rate has not changed significantly in this malignancy during recent decades.MethodsIn this study, we focused on TP53 mutations in specific regions, including DNA-binding surface, to determine whether mutations at specific locations of TP53 could be used to help in setting up prognosis and response to therapy of head and neck squamous cell carcinoma patients. We analysed TP53 mutations in 46 HNSCC by PCR-SSCP and sequencing and characterized how different TP53 mutations affect the patient outcome.ResultsTumours containing TP53 mutations in DNA-binding regions (L2, L3 and LSH motif) had a significantly poorer prognosis and response to radiotherapy than tumours outside those regions. Disease-specific 5-year survival of patients with TP53 mutations affecting DNA contacts was 43.5% while it was 77.8% (p < 0.05) in patients with TP53 mutations in other residues not involved in DNA contact. Moreover, nodal metastasis were more prevalent (although not statistically significantly) with TP53 mutations in DNA-binding surface regions. We noticed that the patients with TP53 mutations in L3/LSH motifs had a significantly poorer response (11.4% responding) to radiation than the patients with a wild type p53 (48.6%) or TP53 mutations outside the DNA-binding regions (40%) (p < 0.05).ConclusionsThese data indicate that a TP53 mutation in L2, L3 or LSH is worth pursuing as a marker for predicting prognosis and response to radiation among HNSCC patients.

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Antioxidant supplements promote tumor formation and growth and confer drug resistance in hepatocellular carcinoma by reducing intracellular ROS and induction of TMBIM1

et al. 2021

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Background Controversy over the benefits of antioxidants supplements in cancers persists for long. Using hepatocellular carcinoma (HCC) as a model, we investigated the effects of exogenous antioxidants N-acetylcysteine (NAC) and glutathione (GSH) on tumor formation and growth. Methods Multiple mouse models, including diethylnitrosamine (DEN)-induced and Trp53KO/C-MycOE-induced HCC models, mouse hepatoma cell and human HCC cell xenograft models with subcutaneous or orthotopic injection were used. In vitro assays including ROS assay, colony formation, sphere formation, proliferation, migration and invasion, apoptosis, cell cycle assays were conducted. Western blot was performed for protein expression and RNA-sequencing to identify potential gene targets. Results In these multiple different mouse and cell line models, we observed that NAC and GSH promoted HCC tumor formation and growth, accompanied with significant reduction of intracellular reactive oxygen species (ROS) levels. Moreover, NAC and GSH promoted cancer stemness, and abrogated the tumor-suppressive effects of Sorafenib both in vitro and in vivo. Exogenous supplementation of NAC or GSH reduced the expression of NRF2 and GCLC, suggesting the NRF2/GCLC-related antioxidant production pathway might be desensitized. Using transcriptomic analysis to identify potential gene targets, we found that TMBIM1 was significantly upregulated upon NAC and GSH treatment. Both TCGA and in-house RNA-sequence databases showed that TMBIM1 was overexpressed in HCC tumors. Stable knockdown of TMBIM1 increased the intracellular ROS; it also abolished the promoting effects of the antioxidants in HCC cells. On the other hand, BSO and SSA, inhibitors targeting NAC and GSH metabolism respectively, partially abrogated the pro-oncogenic effects induced by NAC and GSH in vitro and in vivo. Conclusions Our data implicate that exogenous antioxidants NAC and GSH, by reducing the intracellular ROS levels and inducing TMBIM expression, promoted HCC formation and tumor growth, and counteracted the therapeutic effect of Sorafenib. Our study provides scientific insight regarding the use of exogenous antioxidant supplements in cancers.

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Is there a role for PCR-SSCP among the methods for missense mutation detection of TP53 gene?

Cited by 4 publications

References 106 publications

Evaluation of The Mutagenicity and Oxidative Stress of Fipronil After Subchronic Exposure in Male Albino Rats

Evaluation of The Mutagenicity and Oxidative Stress of Fipronil After Subchronic Exposure in Male Albino Rats

Specific TP53 mutations predict aggressive phenotype in head and neck squamous cell carcinoma: a retrospective archival study

Antioxidant supplements promote tumor formation and growth and confer drug resistance in hepatocellular carcinoma by reducing intracellular ROS and induction of TMBIM1

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