Non-random p53 mutations in pediatric undifferentiated (embryonal) sarcoma of the liver
Non-random p53 mutations in pediatric undifferentiated (embryonal) sarcoma of the liver
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DOI：
10.1016/j.hepres.2006.04.009
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发表时间：
2006-08-01
影响因子：
4.2
通讯作者：
Fukuzawa, Masahiro
中科院分区：
文献类型：
--
作者：
Sangkhathat, Surasak;Kusafuka, Takeshi;Fukuzawa, Masahiro
摘要未分化（胚胎性）肝肉瘤是一种罕见的儿童肝脏肿瘤。其发病机制在很大程度上是未知的，但证据表明其与肝间充质错构瘤（MH）有共同的联系。之前，我们在一例儿童USL中发现了p53突变。最近，又发表了一篇报告，进一步证明了成人病例中p53的改变。在本研究中，我们采用PCR-SSCP和直接测序技术分析了3例儿童USL和2例MH。该研究在所有3例USL中都发现了错义突变，但在MH中没有发现。这些突变仅在肿瘤组织中发现，而在周围的正常肝组织中未发现。突变点分别定位于外显子7 （Gly245Ser）、外显子6 （Arg196Pro）和外显子8 （Arg273Pro）。免疫组织化学检测p53蛋白表达的结果显示，USL患者具有较强的免疫反应性，而MH患者呈阴性。总之，本研究提供了新的数据，提示儿童USL患者p53突变不是随机的遗传事件，很可能参与了USL的肿瘤发生。2006爱思唯尔爱尔兰有限公司版权所有。
Undifferentiated (embryonal) sarcoma of the liver (USL) is a rare hepatic tumor in children. Its pathogenesis is largely unknown, but lines of evidence suggest common links to that of mesenchymal hamartoma of the liver (MH). Previously, we found a p53 mutation in a case of pediatric USL. Recently, there was another published report, demonstrating further evidence of p53 alterations in the adult cases. In this study, we analyzed in three cases of pediatric USL and two cases of MH by using PCR-SSCP and direct sequencing technique. The study identified missense mutations in all three cases of USL, but none of MH. The mutations were found specifically in tumor tissue and not detected in the surrounding normal hepatic tissue. Mutation points were localized in exon 7 (Gly245Ser), exon 6 (Arg196Pro), and exon 8 (Arg273Pro), respectively. Irnmunohistochemical study of p53 protein expression revealed strong immunoreactivity in cases of USL and negative staining in MH. In summary, this study provided a novel data suggesting that mutations of p53 in pediatric USL are not random genetic events and highly possible to be involved in its tumorigenesis. (c) 2006 Elsevier Ireland Ltd. All rights reserved.