Miao Jiangyong, Kusafuka Takeshi, Okada Akira
Department of Pediatric Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Oncol Rep. 2003 Nov-Dec;10(6):1943-6. doi: 10.3892/or.10.6.1943.
The Wnt signaling pathway is conserved in various species from worms to mammals, and plays critical roles in development, cellular proliferation and differentiation. As part of Wnt signal transduction, the function of the Axin complex is inhibited, leading to the accumulation of beta-catenin protein. Axin gene mutations have been detected in several kinds of human cancers. In this study, we investigated Axin gene alterations in a series of 58 pediatric neoplasms including neuroblastomas, teratomas, rhabdomyosarcomas. Forty-eight non-tumor tissues were used as a control series to compare gene alterations and their frequencies between tumors and normal tissues. The whole coding region of the Axin gene was examined by PCR-SSCP method using 24 sets of the primers. Samples revealing aberrant band patterns were subjected to direct sequencing analysis. In total, we identified six variants in the exons and four intronic nucleotide substitutions in the tumor series. Similar sequence variants except a rare sequence variant at codon 98 (CCG right curved arrow CTG) were observed in the control series and these were regarded as non-pathogenetic polymorphisms. Our results indicated that a tumor-associated mutation of the Axin gene is generally a rare event in our series of pediatric neoplasms.
Wnt信号通路在从蠕虫到哺乳动物的各种物种中都是保守的，并且在发育、细胞增殖和分化中起关键作用。作为Wnt信号转导的一部分，轴抑制蛋白复合物的功能受到抑制，导致β-连环蛋白的积累。在几种人类癌症中已经检测到轴抑制蛋白基因的突变。在本研究中，我们调查了一系列58例儿童肿瘤（包括神经母细胞瘤、畸胎瘤、横纹肌肉瘤）中的轴抑制蛋白基因改变。48份非肿瘤组织用作对照系列，以比较肿瘤组织与正常组织之间的基因改变及其频率。使用24组引物通过PCR-SSCP方法检测轴抑制蛋白基因的整个编码区。对显示异常条带模式的样本进行直接测序分析。在肿瘤系列中，我们总共在编码区鉴定出6个变异体和4个内含子核苷酸替换。在对照系列中观察到了相似的序列变异体（密码子98处的一个罕见序列变异体CCG→CTG除外），这些被认为是非致病性多态性。我们的结果表明，在我们的儿童肿瘤系列中，轴抑制蛋白基因的肿瘤相关突变通常是罕见事件。
