Human Tumor Antigens Tn and Sialyl Tn Arise from Mutations in Cosmc

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...

Full description

Saved in:
Bibliographic Details
Published inCancer research (Chicago, Ill.) Vol. 68; no. 6; pp. 1636 - 1646
Main Authors TONGZHONG JU, LANNEAU, Grainger S, LASZIK, Zoltan, BENBROOK, Doris M, HANIGAN, Marie H, CUMMINGS, Richard D, GAUTAM, Tripti, YINGCHUN WANG, BAOYUN XIA, STOWELL, Sean R, WILLARD, Margaret T, WENYI WANG, XIA, Jonathan Y, ZUNA, Rosemary E
Format Journal Article
LanguageEnglish
Published Philadelphia, PA American Association for Cancer Research 15.03.2008
Subjects
Online AccessGet full text

Cover

Loading…
More Information
Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-07-2345