Correlation between EGFR Gene Mutations and Lung Cancer: a Hospital-Based Study

Matam, Kavitha; Goud, Iravathy; Lakshmi, M. A.; Ravi,; Sridhar, Kasi S.; Pr, Vijayanand; Chakravarthy, S. R. Sannasi; Sv, Prasad; Sn, Tabassum; Na, Shaik; Syed, Rabbani; Kk, Alharbi; Khan, I.U.

doi:10.7314/apjcp.2015.16.16.7071

Cited by 8 publications

(3 citation statements)

References 37 publications

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“…Moreover, MED12 mutation pattern also suggests it to be putative oncogene (Perot et al, 2012). Like other oncogenes, majority of MED12 mutations are located recurrently at the same amino acid position (codon 44), suggesting that glycine at codon 44 is mutation hotspot for leiomyomas and its location in evolutionarily conserved nucleotide sequences makes it a putative causal variant (Matam et al, 2015; Wang et al, 2015, 2017). Since, exon2 region falls in Cyclin C-CDK8 binding domain of MED12 protein, it is expected that mutations in this region induce conformational changes in MED12 binding interface of Cyclin C-CDK8 domain, which further negatively influence binding characteristics and stability of CDK8-mediator complex (Banaganapalli et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Expanded Somatic Mutation Spectrum of MED12 Gene in Uterine Leiomyomas of Saudi Arabian Women

et al. 2018

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MED12, a subunit of mediator complex genes is known to harbor genetic mutations, (mostly in exon 2), causal to the genesis of uterine leiomyomas among Caucasian, African American, and Asian women. However, the precise relationship between genetic mutations vs. protein or disease phenotype is not well-explained. Therefore, we sought to replicate the MED12 mutation frequency in leiomyomas of Saudi Arabian women, who represents ethnically and culturally distinct population. We performed molecular screening of MED12 gene (in 308 chromosomes belonging to 154 uterine biopsies), analyzed the genotype-disease phenotype correlations and determined the biophysical characteristics of mutated protein through diverse computational approaches. We discovered that >44% (34/77) leiomyomas of Arab women carry a spectrum of MED12 mutations (30 missense, 1 splice site, and 3 indels). In addition to known codon 44, we observed novel somatic mutations in codons 36, 38, and 55. Most genetically mutated tumors (27/30; 90%) demonstrated only one type of genetic change, highlighting that even single allele change in MED12 can have profound impact in transforming the normal uterine myometrium to leiomyomas. An interesting inverse correlation between tumor size and LH is observed when tumor is positive to MED12 mutation (p < 0.05). Our computational investigations suggest that amino acid substitution mutations in exon-2 region of MED12 might contribute to potential alterations in phenotype as well as the stability of MED12 protein. Our study, being the first one from Arab world, confirms the previous findings that somatic MED12 mutations are critical to development and progression of uterine leiomyomas irrespective of the ethnic background. We recommend that mutation screening, particularly codon 44 of MED12 can assist in molecular diagnostics of uterine leiomyomas in majority of the patients.

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Section: Discussionmentioning

confidence: 99%

Expanded Somatic Mutation Spectrum of MED12 Gene in Uterine Leiomyomas of Saudi Arabian Women

et al. 2018

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“…Tyrosine kinase EGRF (Epidermal Growth Factor Receptor) influences cell proliferation, cell division, and tumour development. It is a representative transmembrane receptor which triggers signalling pathways via ligand-provoked dimerization (Kavitha et al, 2015;Zhou and Yao, 2016;. In human cancers, the most prevalently mutated oncogene is the Kirsten rat sarcoma (KRAS) gene involved in carcinogenesis, which accounts for more than twenty per cent of lung cancer, particularly NSCLC (Reck et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Molecular Level Atomistic and Structural Insights on Biological Macromolecules, Inhibition, and Dynamics Studies

2024

Frontiers Research Topics

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Frontiers is more than just an open access publisher of scholarly articles: it is a pioneering approach to the world of academia, radically improving the way scholarly research is managed. The grand vision of Frontiers is a world where all people have an equal opportunity to seek, share and generate knowledge. Frontiers provides immediate and permanent online open access to all its publications, but this alone is not enough to realize our grand goals. Frontiers journal seriesThe Frontiers journal series is a multi-tier and interdisciplinary set of openaccess, online journals, promising a paradigm shift from the current review, selection and dissemination processes in academic publishing. All Frontiers journals are driven by researchers for researchers; therefore, they constitute a service to the scholarly community. At the same time, the Frontiers journal series operates on a revolutionary invention, the tiered publishing system, initially addressing specific communities of scholars, and gradually climbing up to broader public understanding, thus serving the interests of the lay society, too. Dedication to qualityEach Frontiers article is a landmark of the highest quality, thanks to genuinely collaborative interactions between authors and review editors, who include some of the world's best academicians. Research must be certified by peers before entering a stream of knowledge that may eventually reach the public -and shape society; therefore, Frontiers only applies the most rigorous and unbiased reviews. Frontiers revolutionizes research publishing by freely delivering the most outstanding research, evaluated with no bias from both the academic and social point of view. By applying the most advanced information technologies, Frontiers is catapulting scholarly publishing into a new generation. What are Frontiers Research Topics?Frontiers Research Topics are very popular trademarks of the Frontiers journals series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area.

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“…Tyrosine kinase EGRF (Epidermal Growth Factor Receptor) influences cell proliferation, cell division, and tumour development. It is a representative transmembrane receptor which triggers signalling pathways via ligand-provoked dimerization ( Kavitha et al, 2015 ; Zhou and Yao, 2016 ; Shaik et al, 2019 ). In human cancers, the most prevalently mutated oncogene is the Kirsten rat sarcoma (KRAS) gene involved in carcinogenesis, which accounts for more than twenty per cent of lung cancer, particularly NSCLC ( Reck et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Targeting potential receptor molecules in non-small cell lung cancer (NSCLC) using in silico approaches

Kirubhanand

Leonora²,

Anitha³

et al. 2023

Front. Mol. Biosci.

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Introduction: Non-Small Cell Lung Cancer is the most prevalent type of cancer in lung cancer. Chemotherapy, radiation therapy, and other conventional cancer treatments have a low success rate. Thus, creating new medications is essential to halt the spread of lung cancer.Methods: In this study bioactive nature of lochnericine against Non-Small Cell Lung Cancer (NSCLC) was analyzed using various computational approaches such as quantum chemical calculations, molecular docking, and molecular dynamic simulation. Furthermore, the MTT assay shows the anti-proliferation activity of lochnericine.Results and Discussion: Using Frontier Molecular Orbital (FMO), the calculated band gap energy value associated with bioactive compounds and the molecule’s potential bioactivity is confirmed. The H38 hydrogen atom and O1 oxygen atom in the molecule are effectively electrophilic, and potential nucleophilic attack sites were confirmed through analysis of the Molecular electrostatic potential surface. Furthermore, the electrons within the molecule were delocalized, which confers bioactivity on the title molecule and was authorized through Mulliken atomic charge distribution analysis. A molecular docking study revealed that lochnericine inhibits non-small cell lung cancer-associated targeted protein. The lead molecule and targeted protein complex were stable during molecular dynamics simulation studies till the simulation period. Further, lochnericine demonstrated remarkable anti-proliferative and apoptotic features against A549 lung cancer cells. The current investigation powerfully suggests that lochnericine is a potential candidate for lung cancer.

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Correlation between EGFR Gene Mutations and Lung Cancer: a Hospital-Based Study

Cited by 8 publications

References 37 publications

Expanded Somatic Mutation Spectrum of MED12 Gene in Uterine Leiomyomas of Saudi Arabian Women

Expanded Somatic Mutation Spectrum of MED12 Gene in Uterine Leiomyomas of Saudi Arabian Women

Molecular Level Atomistic and Structural Insights on Biological Macromolecules, Inhibition, and Dynamics Studies

Targeting potential receptor molecules in non-small cell lung cancer (NSCLC) using in silico approaches

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