Cytoskeletal rearrangement occurs in variety of cellular processes and involves a wide spectrum of proteins. Gelsolin super family proteins control actin organization by severing and capping filament ends and nucleating actin assembly. Gelsolin is the founding member of this family and plays important role in pathogenesis of human neoplasia.This study aimed to investigate the germline mutations and expressional profile of Gelsolin in human breast cancer tissues. For germ line screening PCR-SSCP technique was used while expression was analyzed through quantitative real time PCR. Different types of mutations were observed in Gelsolin coding regions on exons 4, 10, 11, 14 and 15. These mutations include 3 missense nonsynonymous substitution mutations, 2 deletions, 1 insertion and 1 synonymous substitution mutation. Gelsolin transcript level was found significantly lower in breast tumor tissues compared to control samples (p=0.03). Low level of Gelsolin was found in metastatic patients (p=0.002) and patients who died from breast cancer (P=0.03) compared to disease free patients at final follow up. This study shows that level of Gelsolin is down regulated in breast cancer tissues and is linked with metastasis development and death in patients. It is concluded that genetic changes in coding regions of Gelsolin can potentially contribute to genetic instability. These genetic variations and expressional correlation with patient survival may prove to be of significant importance.

中文翻译：

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凝溶胶蛋白的突变谱及其下调与乳腺癌有关。

细胞骨架重排发生在各种细胞过程中，涉及广泛的蛋白质。凝溶胶蛋白超家族蛋白通过切断和加盖细丝末端以及使肌动蛋白组装成核来控制肌动蛋白组织。Gelsolin 是该家族的创始成员，在人类肿瘤的发病机制中起重要作用。本研究旨在研究 Gelsolin 在人乳腺癌组织中的种系突变和表达谱。对于种系筛选，使用 PCR-SSCP 技术，同时通过定量实时 PCR 分析表达。在外显子 4、10、11、14 和 15 的凝溶胶蛋白编码区中观察到不同类型的突变。这些突变包括 3 个错义非同义替换突变、2 个缺失、1 个插入和 1 个同义替换突变。p = 0.03）。在最终随访时与无病患者相比，在转移患者 ( p = 0.002) 和死于乳腺癌的患者 ( P = 0.03)中发现凝溶胶蛋白水平较低。该研究表明，凝溶胶蛋白水平在乳腺癌组织中下调，并且与患者的转移发展和死亡有关。结论是凝溶胶蛋白编码区的遗传变化可能导致遗传不稳定性。这些遗传变异和表达与患者存活的相关性可能被证明具有重要意义。