Lack of homozygously inactivated p73 in single-copy MYCN primary neuroblastomas and neuroblastoma cell lines
Lack of homozygously inactivated p73 in single-copy MYCN primary neuroblastomas and neuroblastoma cell lines
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DOI：
10.1038/sj.neo.7900010
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发表时间：
1999-04-01
期刊：
影响因子：
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通讯作者：
Look, A. Thomas
中科院分区：
文献类型：
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作者：
Kong, Xiao-Tang;Valentine, Virginia A.;Look, A. Thomas
我们检查了18个神经母细胞瘤细胞系和32个原发性单拷贝MYCN肿瘤标本，以确定位于染色体带1p36.33的新型p53相关基因p73的突变是否有助于儿童神经母细胞瘤的发生或进展。通过荧光原位杂交，18个细胞系中的16个，但32个原发性肿瘤中只有3个，有证据表明p73等位基因缺失。这些细胞系和肿瘤表达的mRNA中的p73编码区的序列分析没有发现失活突变，表明p73在神经母细胞瘤中不是同源失活的。然而，几种新的剪接形式的p73 mRNA被确定，包括一个没有外显子11，占主导地位的多个MYCN扩增的细胞系。其编码的p73蛋白与其他剪接形式的不同之处在于其C-末端来自一个替代的阅读框架。需要进一步研究这种剪接形式的p73编码的蛋白质的功能特性，以确定它是否有助于MYCN基因扩增的儿童神经母细胞瘤的发病机制。
We examined 18 neuroblastoma cell lines and 32 primary single-copy MYCN tumor specimens to determine whether mutations of p73, a novel p53-related gene located in chromosome band 1p36.33, contribute to the genesis or progression of childhood neuroblastoma. By fluorescence in situ hybridization, 16 of the 18 cell lines, but only 3 of the 32 primary tumors, had evidence of a deleted p73 allele. Sequence analysis of the p73 coding region in the mRNAs expressed by these cell lines and tumors did not reveal inactivating mutations, suggesting that p73 is not homozygously inactivated in neuroblastoma. However, several novel splice forms of p73 mRNAs were identified, including one without exon 11 that predominated in multiple MYCN-amplified cell lines. Its encoded p73 protein differed from other splice forms in that the C-terminus was derived from an alternative reading frame. Further study of the functional properties of the protein encoded by this splice form of p73 will be needed to determine whether it contributes to the pathogenesis of childhood neuroblastoma with MYCN gene amplification.