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首页> 外文期刊>Mutation research-Fundamental and Molecular Mechanisms of Mutagenesis >Mutational pressure and natural selection in epidermal growth factor receptor gene during germline and somatic mutagenesis in cancer cells
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Mutational pressure and natural selection in epidermal growth factor receptor gene during germline and somatic mutagenesis in cancer cells

机译：根形生长因子受体基因的突变压力和自然选择在癌细胞中的种系和体细胞诱变期间

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摘要

In this study we investigated nucleotide usage biases along the length of a gene encoding human epidermal growth factor receptor (EGFR) and found out that there had been mutational GC-pressure with stronger asymmetric C-pressure in that gene before the preferable direction of nucleotide mutations changed. Current preferable direction of germline mutations in EGFR gene has been estimated with the help of Ensembl data base of gene variations. Preferable direction of somatic mutations in EGFR gene from cancer cells has been estimated with the help of COSMIC data base. Both germline and somatic mutations in cancer cells have the same GC to AT preferable direction in EGFR gene. These data have been used with the aim to find fragments of EGFR gene that have lower probability of missense C to T and G to A transitions to occur. So, the less mutable parts of extracellular EGFR domain are: C-terminal part of the first beta barrel and the central part of the second beta barrel. The less mutable parts of tyrosine kinase EGFR domain are: ATP-binding site (partially), regulatory alpha helix, and fragments that change their secondary structure during the activation process. These parts of EGFR should be considered as the best targets for new types of therapy development. Such criterion as low mutability is especially important for the selection of targets for anti-tumor therapy, since we have detected positive selection of amino acid replacements during somatic mutagenesis of EGFR gene in cancer cells.
机译：在这项研究中，我们研究了编码人表皮生长因子受体（EGFR）的基因的长度的核苷酸使用偏差，并发现在核苷酸突变的优选方向之前，在该基因中具有较强的不对称C压力的突变GC压力改变了。借助基因变化的Ensembl数据碱基估计了EGFR基因中的种系突变的目录方向。在宇宙数据群的帮助下估计了从癌细胞中的EGFR基因中的体细胞突变的优选方向。癌细胞中的种系和体细胞突变在EGFR基因中具有相同的GC至优选方向。这些数据已被用于寻找EGFR基因的片段，其将畸形C至T和G的概率较低到要发生的过渡。因此，细胞外EGFR结构域的较差部分是：第一β筒的C末端部分和第二β筒的中心部分。酪氨酸激酶EGFR结构域的较小骨骼部分是：ATP结合位点（部分），调节α螺旋和在激活过程中改变其二级结构的片段。这些部分EGFR应被视为新型治疗发展的最佳目标。这种标准作为低变形性对于选择抗肿瘤疗法的目标尤为重要，因为我们已经检测到在癌细胞中EGFR基因的体细胞诱变期间氨基酸置换的阳性选择。

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