Marzouq Maryam, Nairouz Ali, Ben Khalaf Noureddine, Bourguiba-Hachemi Sonia, Quaddorah Raed, Ashoor Dana, Fathallah M Dahmani
Department of Life Sciences, Health Biotechnology Program, College of Graduate Studies, Arabian Gulf University, PO Box 26671, Manama, Kingdom of Bahrain.
King Fahad Chair for Health Biotechnology, College of Graduate Studies, Arabian Gulf University, PO Box 26671, Manama, Kingdom of Bahrain.
BMC Res Notes. 2021 Apr 19;14(1):146. doi: 10.1186/s13104-021-05559-y.
This study aimed to identify novel genetic variants in the CR2 extracellular domain of the epidermal growth factor receptor (EGFR) in healthy individuals and patients with six different types of adenocarcinoma, in Arabian peninsula populations. It also aimed to investigate the effects of these variants on the EGFR structure and their eventual relevance to tumorigenesis.
We detected seven new EGFR genetic variants in 168 cancer patients and 114 controls. A SNP rs374670788 was more frequent in bladder cancer but not significantly associated to. However, a missense mutation (V550M) was significantly associated to colon, ovary, lung, bladder and thyroid cancer samples (p < 0.05). Three mutations (H590R, E602K and T605T) were found in the heterozygous form only in colon cancer patients. Genomic analysis of the synonymous mutation (G632G) showed that the T/A genotype could be associated to thyroid cancer in Arab patients (p < 0.05). An additional novel SNP rs571064657 was observed in control individuals. Computational analysis of the genetic variants revealed a reduction in the stabilization of the EGFR tethered form for both V550M and the common R521K variant with low energetic state (- ∆∆G). Molecular interactions analysis suggested that these mutations might affect the receptor's function and promote tumorigenesis.
本研究旨在识别阿拉伯半岛人群中健康个体及六种不同类型腺癌患者的表皮生长因子受体（EGFR）CR2胞外域的新型基因变异。本研究还旨在调查这些变异对EGFR结构的影响及其与肿瘤发生的最终相关性。
我们在168例癌症患者和114例对照中检测到7种新的EGFR基因变异。单核苷酸多态性rs374670788在膀胱癌中更常见，但无显著相关性。然而，一个错义突变（V550M）与结肠癌、卵巢癌、肺癌、膀胱癌和甲状腺癌样本显著相关（p < 0.05）。三个突变（H590R、E602K和T605T）仅在结肠癌患者中以杂合形式被发现。同义突变（G632G）的基因组分析表明，T/A基因型可能与阿拉伯患者的甲状腺癌相关（p < 0.05）。在对照个体中观察到另一个新的单核苷酸多态性rs571064657。对基因变异的计算分析显示，V550M和常见的R521K变异在低能量状态（-∆∆G）下，EGFR栓系形式的稳定性均降低。分子相互作用分析表明，这些突变可能影响受体功能并促进肿瘤发生。
