Identification of a new cancer/testis gene family, CT47, among expressed multicopy genes on the human X chromosome

Identification of a new cancer/testis gene family, CT47, among expressed multicopy genes on the human X chromosome
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DOI:
10.1002/gcc.20298
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发表时间:
2006-04-01
影响因子:
3.7
通讯作者:
Jongeneel, CV
Jongeneel, CV
中科院分区:
医学2区
文献类型:
--
作者:
Chen, YT;Iseli, C;Jongeneel, CV

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癌症/睾丸(CT)基因通常仅在生殖细胞中表达,但在某些肿瘤中被重新激活并表达。在迄今为止鉴定的大约40个CT基因或基因家族中,有20个位于X染色体上,并且作为多基因家族存在,其中许多具有高度保守的成员。这表明通过检测X染色体上重复表达的基因可以鉴定新的CT基因家族。通过搜索映射到染色体上多个位置的转录簇,然后对其基因表达谱进行计算机分析,我们鉴定了5个具有睾丸特异性表达且家族成员之间序列同一性> 98%的新基因家族。通过定性和定量RT-PCR检测了这些基因在正常组织和各种肿瘤细胞系及标本中的表达,并在Xq 24上鉴定了一个至少具有13个拷贝的新CT基因家族,命名为CT 47。CT 47 mRNA主要在睾丸中表达,在胎盘中表达较弱。脑组织是测试的唯一阳性体组织,估计CT 47转录水平为睾丸中发现的0.09%。在检测的肿瘤标本中,在肺癌和食管癌标本中发现了类似于15%的CT 47表达,但在结直肠癌和乳腺癌中没有发现。推定的CT 47蛋白由288个氨基酸残基组成,具有富含丙氨酸和谷氨酸的C-末端。除了人类之外,唯一检测到与CT 47同源的基因的物种是黑猩猩,预测的蛋白质在其羧基末端区域显示出类似于80%的同一性。(c)2005 Wiley-Liss,Inc.
Cancer/testis (CT) genes are normally expressed in germ cells only, yet are reactivated and expressed in some tumors. Of the approximately 40 CT genes or gene families identified to date, 20 are on the X chromosome and are present as multigene families, many with highly conserved members. This indicates that novel CT gene families may be identified by detecting duplicated expressed genes on chromosome X. By searching for transcript clusters that map to multiple locations on the chromosome, followed by in silico analysis of their gene expression profiles, we identified five novel gene families with testis-specific expression and > 98% sequence identity among family members. The expression of these genes in normal tissues and various tumor cell lines and specimens was evaluated by qualitative and quantitative RT-PCR, and a novel CT gene family with at least 13 copies was identified on Xq24, designated as CT47. mRNA expression of CT47 was found mainly in the testes, with weak expression in the placenta. Brain tissue was the only positive somatic tissue tested, with an estimated CT47 transcript level 0.09% of that found in testis. Among the tumor specimens tested, CT47 expression was found in similar to 15% of lung cancer and esophageal cancer specimens, but not in colorectal cancer or breast cancer. The putative CT47 protein consists of 288 amino acid residues, with a C-terminus rich in alanine and glutamic acid. The only species other than human in which a gene homologous to CT47 has been detected is the chimpanzee, with the predicted protein showing similar to 80% identity in its carboxy terminal region. (c) 2005 Wiley-Liss, Inc.