Genetic and epigenetic alterations of the EGFR and mutually independent association with BRCA1, MGMT, and RASSF1A methylations in Vietnamese lung adenocarcinomas

Nguyễn, Quang Ngọc; Vuong, Linh Dieu; Truong, Van-Long; Ta, To Van; Nguyen, Nam Trung; Nguyen, Hung Phi; Chu, Ha Hoang

doi:10.1016/j.prp.2019.01.032

Cited by 11 publications

(5 citation statements)

References 44 publications

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“…It is well known that lung adenocarcinomas with or without EGFR mutations have shown different drug effects against EGFR inhibitors. But EGFR is an oncogene; the abnormality of its related pathways is closely associated with tumor development, invasion, metastasis and drug resistance [1][2][3][4][16][17][18][19]. Up till now it remains unclear and controversial whether there is a difference in malignant degree and prognosis between patients with EGFR mutations and those without mutations.…”

Section: Discussionmentioning

confidence: 99%

The Correlation between EGFR Mutation Status and DNA Content of Lung Adenocarcinoma Cells in Pleural Effusion

Guo

Wang

et al. 2020

J. Cancer

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Objectives: Lung adenocarcinomas with or without epidermal growth factor receptor (EGFR) mutations have shown different drug effects against EGFR inhibitors. But it is not very clear if EGFR mutation status affects the biological behavior of lung adenocarcinoma, because tumor gene regulation is very complicated and can be affected by many factors. We aimed to explore if EGFR mutation status is related with tumor malignant degree by investigating the relevance of EGFR mutation status with DNA content and aneuploid peaks of lung adenocarcinoma cells in pleural fluids without using EGFR-TKIs. Materials and Methods: 591 cases of lung adenocarcinoma patients in Hebei Tumor Hospital who had undergone EGFR gene detection and DNA quantitative analysis were collected from January 2012 to August 2018.They were divided into two groups: EGFR mutant group and non-mutant group. EGFR mutations were detected by Amplification Refractory Mutation System (ARMS) and ABI 7500 Fluorescence quantitative PCR with pleural effusions. DNA content and aneuploid peaks were detected by LD DNA image cytometry (DNA-ICM). Rank-sum test of SPSS 16 was used for statistical analysis. Results: The maximum DI, the mean DI of the first 20 cells greater than 5C, the percentage of cells greater than 5C and the number of cells greater than 9C of the first 20 cells in the mutant group were all higher than those in the non-mutant group, having statistical significance (p<0.001); the peaks of aneuploid cells in the mutant group occurred more often than those in the non-mutant group, having statistical significance (p<0.001). Conclusions: Our study has shown that advanced lung adenocarcinomas with EGFR-mutations had higher DI values, more aneuploid cells and more frequent aneuploid peaks compared with those without EGFR-mutations, suggesting that advanced lung adenocarcinomas with EGFR mutations are more aggressive than those without EGFR mutations.

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Section: Discussionmentioning

confidence: 99%

The Correlation between EGFR Mutation Status and DNA Content of Lung Adenocarcinoma Cells in Pleural Effusion

Guo

Wang

et al. 2020

J. Cancer

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“…However, most studies (19/21, 90.5%) were judged as having either a high or unclear risk of bias regarding the methylation analyses due to absence or unclear information on blinding, thresholds and controls [481]. Brca1 and Mgmt promoter hypermethylation are not limited to breast cancer but are observed in other malignancies such as lung adenocarcinoma [482]. Interestingly, sodium arsenite exposure was shown to increase Brca1 promoter methylation in the human breast cancer cell line MCF7 in vitro [313], supporting that it may be a useful marker.…”

Section: Brca1 H2ax and H4k20mentioning

confidence: 99%

Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications

Desaulniers

Vasseur

Jacobs

et al. 2021

IJMS

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Epigenetics involves a series of mechanisms that entail histone and DNA covalent modifications and non-coding RNAs, and that collectively contribute to programing cell functions and differentiation. Epigenetic anomalies and DNA mutations are co-drivers of cellular dysfunctions, including carcinogenesis. Alterations of the epigenetic system occur in cancers whether the initial carcinogenic events are from genotoxic (GTxC) or non-genotoxic (NGTxC) carcinogens. NGTxC are not inherently DNA reactive, they do not have a unifying mode of action and as yet there are no regulatory test guidelines addressing mechanisms of NGTxC. To fil this gap, the Test Guideline Programme of the Organisation for Economic Cooperation and Development is developing a framework for an integrated approach for the testing and assessment (IATA) of NGTxC and is considering assays that address key events of cancer hallmarks. Here, with the intent of better understanding the applicability of epigenetic assays in chemical carcinogenicity assessment, we focus on DNA methylation and histone modifications and review: (1) epigenetic mechanisms contributing to carcinogenesis, (2) epigenetic mechanisms altered following exposure to arsenic, nickel, or phenobarbital in order to identify common carcinogen-specific mechanisms, (3) characteristics of a series of epigenetic assay types, and (4) epigenetic assay validation needs in the context of chemical hazard assessment. As a key component of numerous NGTxC mechanisms of action, epigenetic assays included in IATA assay combinations can contribute to improved chemical carcinogen identification for the better protection of public health.

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“…ERBB4, EGFR, and EP300 belong to the same HER2 signal transduction pathway, and although the exact clinical relevance of the aforementioned genes is still partly unknown, the activation of ERBB3 and PI3K signaling contributes to acquired resistance to tyrosine kinase inhibitors targeting EGFR and HER2 in lung and breast cancer [18]. According to a recent study on lung adenocarcinoma patients, a positive correlation might exist between EGFR and BRCA1 methylation but not EGFR mutation, and epigenetic modifications of BRCA1 are independent events against EGFR mutation [19]. However, no data are available regarding the association between the aforementioned mutations in SCLC.…”

Section: Discussionmentioning

confidence: 99%

Next-Generation Sequencing May Discriminate Extreme Long-term versus Short-term Survival in Patients with Metastatic Small Cell Lung Cancer (SCLC)

Lohinai

Döme

Weiss³

2019

Translational Oncology

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BACKGROUND: Molecular underpinnings that may prognosticate survival could increase understanding of small cell lung cancer (SCLC) tumor behavior. Here, we report the clinicopathological characteristics and biomarker profiles of short-term (ST) versus long-term (LT) survival in patients with metastatic SCLC. METHODS: Of the 876 consecutive metastatic SCLC patients receiving standard of care therapy, 44 met the definition of LT and 91 for ST, respectively. Available FFPE tumor tissue blocks were analyzed by next-generation sequencing (NGS). Analysis included gene mutations, copy number variations, mRNA expression, and protein expression by immunohistochemistry, followed by correlation with clinicopathological characteristics. RESULTS: There were no statistically significant and clinically relevant differences in cases with or without FFPE according to major clinicopathological variables in ST and LT. However, according to NGS, five mutually exclusive gene mutations were identified (E1A binding protein P300 [EP300] p.N217S; p.E152K; human epidermal growth factor receptor 4 [ERBB4] p.E317K; BRCA1, DNA repair associated [BRCA1] p.E1661N, and epidermal growth factor receptor [EGFR] p.V742A). Comparing LT vs. ST survivals, a twofold increase was found in the average predicted number of drugs per patient off compendium. We found high SSTR2 mRNA expressions in all LT patients (vs. two [20%] ST patients), which may reflect more benign neuroendocrine tumor characteristics. CONCLUSIONS: Consolidation radiation therapy and higher predicted drug sensitivity for off compendium were associated with LT compared to ST patients in SCLC. NGS profiling of extreme survivals may improve classification of SCLC and possibly identify clinically relevant new targets.

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Genetic and epigenetic alterations of the EGFR and mutually independent association with BRCA1, MGMT, and RASSF1A methylations in Vietnamese lung adenocarcinomas

Cited by 11 publications

References 44 publications

The Correlation between EGFR Mutation Status and DNA Content of Lung Adenocarcinoma Cells in Pleural Effusion

The Correlation between EGFR Mutation Status and DNA Content of Lung Adenocarcinoma Cells in Pleural Effusion

Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications

Next-Generation Sequencing May Discriminate Extreme Long-term versus Short-term Survival in Patients with Metastatic Small Cell Lung Cancer (SCLC)

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