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 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.
Ju
Tongzhong
T
Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322, USA. tju@emory.edu
Lanneau
Grainger S
GS
Gautam
Tripti
T
Wang
Yingchun
Y
Xia
Baoyun
B
Stowell
Sean R
SR
Willard
Margaret T
MT
Wang
Wenyi
W
Xia
Jonathan Y
JY
Zuna
Rosemary E
RE
Laszik
Zoltan
Z
Benbrook
Doris M
DM
Hanigan
Marie H
MH
Cummings
Richard D
RD
D015295:Antigens, Tumor-Associated, Carbohydrate / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D005260:Female; D005700:Galactosyltransferases / Q000172:deficiency / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008545:Melanoma / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D018832:Molecular Chaperones / Q000235:genetics* / Q000276:immunology; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000276:immunology*; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000235:genetics / Q000276:immunology
D015295:Antigens, Tumor-Associated, Carbohydrate; C505369:C1GALT1C1 protein, human; D018832:Molecular Chaperones; C040286:Tn antigen; C055491:sialosyl-Tn antigen; C505293:C1GALT1 protein, human; D005700:Galactosyltransferases