Association between Smoking and p53 Mutation in Lung Cancer: A Meta-analysis

Liu, X.; Lin, Xiaoqing; Wang, C.P.; Yan, Kangkang; Zhao, Lanfei; An, Wei; Liu, X.D.

doi:10.1016/j.clon.2013.09.003

Cited by 36 publications

(28 citation statements)

References 35 publications

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“…In addition, the TP53 mutation is associated with smoking-induced lung cancer. Smokers with lung cancer have a higher risk of TP53 mutation than non-smokers (22). However, our current data shed little light on the question of whether SWI/SNF mutations are associated with smokers in lung cancer.…”

Section: Discussioncontrasting

confidence: 42%

Loss of function of SWI/SNF chromatin remodeling genes leads to genome instability of human lung cancer

et al. 2014

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Abstract. SWI/SNF chromatin remodeling complexes are frequently mutated in a variety of human cancers. We investigated the mutation incidence and the role of mSWI/SNF (BAF) complexes in human lung cancer. In the present study, we analyzed somatic mutations of BAF complexes and other driver mutated genes of lung carcinoma deposited in the Catalogue of Somatic Mutations in Cancer (COSMIC) database. BAF complexes were mutated in 282 of 803 (35.12%) lung carcinoma samples analyzed, ranking second to TP53. Significantly, BAF-mutated samples exhibited more genomic mutations than BAF wild-type ones. Moreover, a significant positive correlation existed between the BAF mutations and overall genomic mutations in these lung carcinoma samples (P<0.001, Pearson's correlation analysis). Specifically, the mutant-typing of 6 BAF genes, SMARCA4, ARID2, ARID1B, BCL11A, BCL11B and BRD9 was associated with more overall mutations in the lung carcinoma samples. A mutation reporter system was developed by means of the establishment of stable cell sublines with slippage-luciferase transcript in a lung adenocarcinoma cell line, Calu-3. SMARCA4, the most frequently mutated BAF gene in lung cancer, was stably knocked down by pSUPER constructs carrying short hairpin RNA (shRNA). Mutation ratios determined from the mutation reporters of Calu-3 cells were significantly increased upon stable SMARCA4 knockdown. We demonstrated that genetic mutations of BAF complexes lead to genome instability of lung carcinoma. Therefore, BAF complexes play an important role in maintaining genome stability in human lung cancer.

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Section: Discussioncontrasting

confidence: 42%

Loss of function of SWI/SNF chromatin remodeling genes leads to genome instability of human lung cancer

et al. 2014

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“…Genetically, carcinogenesis involves multiple processes by which the activation of oncogenes and the inactivation of tumor suppressor genes represent central factors for tumor development and progression of the disease [33]. Tumor suppressor mutations, as reported in LC cells, may contribute to the pathogenesis of invasive cancer [12]. p53 is widely known as a tumor suppressor, while wild-type p53 has been linked with apoptosis, cell cycle arrest, and DNA repair [34].…”

Section: Discussionmentioning

confidence: 99%

“…Recent evidence has revealed that the pattern and frequency of p53 mutations vary among cancer populations depending on the geographical origin. LC commonly presents with p53 gene mutations [12], with 81% of squamous cell carcinoma as well as 46% of lung adenocarcinoma patients carrying a p53 mutation. Likewise, reports have indicated there to exist a high mutation rate in hotspot regions [13].…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic Reticulum Stress Promotes Autophagy and Apoptosis and Reduces Chemotherapy Resistance in Mutant p53 Lung Cancer Cells

Gan

Zhou

Zhong

et al. 2017

Cell Physiol Biochem

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Background/Aims: Lung cancer (LC) continues to be one of the most prevalent cancers around the world. During this study we aimed to investigate the involvement of endoplasmic reticulum stress (ERS) in autophagy, apoptosis, and chemotherapy resistance of mutant p53 LC cells. Methods: Immunohistochemistry was employed to help determine the p53 mutation status of cancer cells from 92 primary LC patients, who were subsequently assigned to either the mutant p53 (n = 39) or wild-type p53 group (n = 53). Results: Mutant p53 cells exhibited increased expression of the C/EBP homologous protein (CHOP), glucose-regulated protein 78 (GRP78), and inositol-requiring enzyme-1α (IRE1α). The Mutant p53 cells were also found to be sensitive to chemotherapy and displayed decreased expression of PI3K, Akt, and mTOR. The mutant p53 cell lines were treated with tunicamycin to induce ERS and rapamycin in order to inhibit mTOR. Both agents increased the expression of CHOP, GRP78, IRE1α, LC3-II/LC3-I, Atg5, Atg7, caspase-3, caspase-12, cleaved caspase-3, cleaved caspase-12, as well as decreases in cell proliferation as well as the expression levels of PI3K, Akt, and mTOR. Enhanced levels of cell apoptosis and reduced chemotherapy resistance were also detected. Conclusion: The findings of our study suggest that ERS promotes autophagy and apoptosis, while acting to reduce chemotherapy resistance in mutant p53 LC cells by downregulating the PI3K/Akt/mTOR signaling pathway.

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“…Most somatic mutations are inactivating mutations (missense and nonsense mutations). The lack of difference in smoking habits (over 5 pack-years) among tumor subtypes (96% [50]) in laryngeal, 69% in oral cavity, 64% in oropharyngeal and 67% in hypopharyngeal HNSCC) fails to explain the difference in TP53 mutations.However, there is a significant difference in HPV infection among subsites (10% HPV+ rate in oral cavity, 62% in oropharyngeal, 7% in laryngeal and 50% in hypopharyngeal HNSCC, p = 4.10E − 12) [51]. TP53 mutations in HPV− tumors only across subsites showed no difference, suggesting that mutation profile depends more on HPV than tumor subtype, which is consistent with different oncogenetic processes.…”

Section: Mutational Profiles In Specific Clinical Conditionsmentioning

confidence: 80%