Mutation analyses of the NFAT1 gene in chondrosarcomas and enchondromas
Mutation analyses of the NFAT1 gene in chondrosarcomas and enchondromas
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DOI：
10.1016/s0304-3835(02)00106-4
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发表时间：
2002-12-01
期刊：
影响因子：
9.7
通讯作者：
Toguchida, J
中科院分区：
文献类型：
--
作者：
Aoyama, T;Nagayama, S;Toguchida, J
缺乏活化T细胞核因子I（NFAT 1）的小鼠表现出关节软骨中软骨细胞的异常增殖，并形成类似于肿瘤病变的骨外软骨肿块，这表明NFAT 1基因是软骨肿瘤中的肿瘤抑制基因。在这里，我们进行了突变分析的NFAT 1基因在人类软骨肿瘤，包括30软骨肉瘤和15内生软骨瘤。逆转录-聚合酶链反应（PCR）分析显示，NFAT 1基因的表达在15/15软骨肉瘤和12/13内生软骨瘤。为了发现细微的改变，使用人类基因组草图序列确定NFAT 1基因的基因组结构，并使用逐外显子PCR-单链构象多态性方法进行突变分析。在8例肿瘤标本中发现了两个杂合错义突变，即A1557 T（His 446 Leu）和C2859 T（Pro 880 Leu），但在相应患者的组成细胞中也存在相同的突变。患者组和对照组中突变等位基因的发生率无显著差异，表明这些突变是与肿瘤发生无关的罕见单核苷酸多态性。这些结果表明，NFAT I基因是不可能是一个肿瘤抑制基因在人类软骨肿瘤。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
Mice lacking nuclear factor of activated T cell I (NFAT1 ) showed an abnormal proliferation of chondrocytes in articular cartilage and formed an extraosseous cartilaginous mass resembling a neoplastic lesion, suggesting that the NFAT1 gene is a tumor suppressor gene in cartilaginous neoplasms. Here we performed mutation analyses of the NFAT1 gene in human cartilaginous tumors including 30 chondrosarcomas and 15 enchondromas. Reverse transcription-polymerase chain reaction (PCR) analysis revealed the expression of the NFAT1 gene in 15/15 chondrosarcomas and 12/13 enchondromas. To find subtle alterations, the genomic structure of the NFAT1 gene was determined using human genome draft sequences, and a mutation analysis was performed using the exon-by-exon PCR-single-strand conformation polymorphism method. Two heterozygous missense mutations, Al557T (His446Leu) and C2859T (Pro880Leu), were found in eight tumor samples, but the same mutation was also present in the constitutional cells of corresponding patients. The incidence of the mutant alleles in the patient and control groups showed no significant difference, suggesting that these mutations are rare single nucleotide polymorphisms unrelated with tumorigenesis. These results suggest that the NFAT I gene is not likely to be a tumor suppressor gene in human cartilaginous tumors. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.