Investigating the Function of Three Non-Synonymous SNPs in EGFR Gene: Structural Modelling and Association With Breast Cancer
Investigating the Function of Three Non-Synonymous SNPs in EGFR Gene: Structural Modelling and Association With Breast Cancer
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DOI：
10.1007/s10930-009-9221-0
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发表时间：
2010-01-01
期刊：
影响因子：
3
通讯作者：
Rebai, Ahmed
中科院分区：
文献类型：
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作者：
Choura, Mouna;Frikha, Fakher;Rebai, Ahmed
非同义单核苷酸多态性（nsSNP）代表改变蛋白质序列和功能的常见基因组变异。据报道，一些影响保守氨基酸的nsSNP与癌症易感性相关。有趣的是，表皮生长因子受体（EGFR）通常在许多癌症中过表达和突变。在这项研究中，我们研究了三个有害的nsSNPs的结构效应：rs17337451（R962G），rs1140476（R977C）和rs17290699（H988P）在EGFR使用计算工具。模型化的突变体二聚体显示出比野生型EGFR二聚体更低的稳定性。此外，我们还发现了R962和H988残基在EGFR二聚体形成中的重要作用。我们还报告了SNP R977C的初步实验数据，表明变异C977可能会增加乳腺癌的风险。这些结果有助于提高对EGFR二聚体稳定性的理解，并为理解EGFR与癌症之间的关系提供了新的元素。
Non-synonymous single nucleotide polymorphisms (nsSNPs) represent common genomic variations that alter protein sequence and function. Some nsSNPs affecting conserved amino acids have been reported to be associated with cancer susceptibility. Interestingly, Epidermal Growth Factor Receptor (EGFR) is commonly overexpressed and mutated in many cancers. In this study, we investigated the structural effect of three deleterious nsSNPs: rs17337451 (R962G), rs1140476 (R977C) and rs17290699 (H988P) within EGFR using computational tools. The modelled mutant dimers showed less stability than wild type EGFR dimer. Furthermore, we showed the important role of R962 and H988 residues in the EGFR dimer formation. We also report preliminary experimental data for SNP R977C suggesting that the variant C977 might confer greater risk for breast cancer. These results contribute to an improved understanding of the EGFR dimer stability and provide new elements for understanding the relationship between EGFR and cancer.