Human tumor antigens to and sialyl Tn arise from mutations in Cosmc
Human tumor antigens to and sialyl Tn arise from mutations in Cosmc
复制标题
DOI：
10.1158/0008-5472.can-07-2345
复制
发表时间：
2008-03-15
期刊：
影响因子：
11.2
通讯作者：
Cummings, Richard D.
中科院分区：
文献类型：
--
作者：
Ju, Tongzhong;Lanneau, Grainger S.;Cummings, Richard D.
肿瘤性病变通常表达糖脂、粘蛋白和其他糖蛋白上的特异性碳水化合物抗原。这些抗原通常处于表观遗传控制之下，并且在治疗选择压力下会发生逆转和丢失。我们在这里报告，两个最常见的肿瘤相关的碳水化合物抗原，Tn和唾液酸Tn（STn），导致体细胞突变的基因Cosmc，编码所需的活性T-合成酶的形成的分子伴侣。不同的肿瘤病变，包括结肠癌和黑色素瘤衍生的细胞系，表达Tn和STn抗原由于Cosmc的功能丧失突变。此外，还发现两个显示Tn/STn抗原表达的人宫颈癌标本存在Cosmc突变和交联Cosmc基因座杂合性缺失。这是第一个在多种类型的癌症中引起细胞表面碳水化合物抗原表达整体改变的体细胞突变的例子。
Neoplastic lesions typically express specific carbohydrate antigens on glycolipids, mucins, and other glycoproteins. Such antigens are often under epigenetic control and are subject to reversion and loss upon therapeutic selective pressure. We report here that two of the most common tumor-associated carbohydrate antigens, Tn and sialyl Tn (STn), result from somatic mutations in the gene Cosmc that encodes a molecular chaperone required for formation of the active T-synthase. Diverse neoplastic lesions, including colon cancer and melanoma-derived cells lines, expressed both Tn and STn antigen due to loss-of-function mutations in Cosmc. In addition, two human cervical cancer specimens that showed expression of the Tn/STn antigens were also found to have mutations in Cosmc and loss of heterozygosity for the cross-linked Cosmc locus. This is the first example of somatic mutations in multiple types of cancers that cause global alterations in cell surface carbohydrate antigen expression.