Institut for Biomedicin

Lars Bolund

Influence of Lewis alpha1-3/4-L-fucosyltransferase (FUT3) gene mutations on enzyme activity, erythrocyte phenotyping, and circulating tumor marker sialyl-Lewis a levels

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Standard

Influence of Lewis alpha1-3/4-L-fucosyltransferase (FUT3) gene mutations on enzyme activity, erythrocyte phenotyping, and circulating tumor marker sialyl-Lewis a levels. / Orntoft, T F; Vestergaard, E M; Holmes, Esbern; Jakobsen, J S; Grunnet, N; Mortensen, M; Johnson, P; Bross, P; Gregersen, N; Andresen, Kirsten Skorstengaard; Jensen, Uffe Birk; Bolund, L; Wolf, H.

I: Journal of Biological Chemistry, Bind 271, Nr. 50, 13.12.1996, s. 32260-8.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Orntoft, TF, Vestergaard, EM, Holmes, E, Jakobsen, JS, Grunnet, N, Mortensen, M, Johnson, P, Bross, P, Gregersen, N, Andresen, KS, Jensen, UB, Bolund, L & Wolf, H 1996, 'Influence of Lewis alpha1-3/4-L-fucosyltransferase (FUT3) gene mutations on enzyme activity, erythrocyte phenotyping, and circulating tumor marker sialyl-Lewis a levels', Journal of Biological Chemistry, bind 271, nr. 50, s. 32260-8.

APA

Orntoft, T. F., Vestergaard, E. M., Holmes, E., Jakobsen, J. S., Grunnet, N., Mortensen, M., Johnson, P., Bross, P., Gregersen, N., Andresen, K. S., Jensen, U. B., Bolund, L., & Wolf, H. (1996). Influence of Lewis alpha1-3/4-L-fucosyltransferase (FUT3) gene mutations on enzyme activity, erythrocyte phenotyping, and circulating tumor marker sialyl-Lewis a levels. Journal of Biological Chemistry, 271(50), 32260-8.

CBE

Orntoft TF, Vestergaard EM, Holmes E, Jakobsen JS, Grunnet N, Mortensen M, Johnson P, Bross P, Gregersen N, Andresen KS, Jensen UB, Bolund L, Wolf H. 1996. Influence of Lewis alpha1-3/4-L-fucosyltransferase (FUT3) gene mutations on enzyme activity, erythrocyte phenotyping, and circulating tumor marker sialyl-Lewis a levels. Journal of Biological Chemistry. 271(50):32260-8.

MLA

Vancouver

Orntoft TF, Vestergaard EM, Holmes E, Jakobsen JS, Grunnet N, Mortensen M o.a. Influence of Lewis alpha1-3/4-L-fucosyltransferase (FUT3) gene mutations on enzyme activity, erythrocyte phenotyping, and circulating tumor marker sialyl-Lewis a levels. Journal of Biological Chemistry. 1996 dec 13;271(50):32260-8.

Author

Orntoft, T F ; Vestergaard, E M ; Holmes, Esbern ; Jakobsen, J S ; Grunnet, N ; Mortensen, M ; Johnson, P ; Bross, P ; Gregersen, N ; Andresen, Kirsten Skorstengaard ; Jensen, Uffe Birk ; Bolund, L ; Wolf, H. / Influence of Lewis alpha1-3/4-L-fucosyltransferase (FUT3) gene mutations on enzyme activity, erythrocyte phenotyping, and circulating tumor marker sialyl-Lewis a levels. I: Journal of Biological Chemistry. 1996 ; Bind 271, Nr. 50. s. 32260-8.

Bibtex

@article{28cb169028b642d6a5570fabf4d794bf,
title = "Influence of Lewis alpha1-3/4-L-fucosyltransferase (FUT3) gene mutations on enzyme activity, erythrocyte phenotyping, and circulating tumor marker sialyl-Lewis a levels",
abstract = "Fucosylated glycoproteins carrying alpha1-4 fucose residues are of importance for cell adhesion and as tumor markers. The Lewis gene, FUT3, encodes the only known alpha1-4-fucosyltransferase (FucT), and individuals who are deficient in this enzyme type as Lewis-negative on erythrocytes. We examined the mutational spectrum of the Lewis gene in Denmark and found 6 different mutations. Five, T59G, T202C, C314T, G508A, and T1067A, were frequent, and one, C445A, was only detected in one out of 40 individuals. Allele-specific polymerase chain reaction as well as cloning of FUT3 alleles showed that the 202 and 314 mutations were co-located on the same allele. COS7 cells transfected with an allele having the 202/314 mutations lacked enzyme activity. Polymerase chain reaction-cleavage assays were established for the genotyping of healthy individuals as well as 20 genuine Lewis-negative cancer patients and 10 non-genuine. The latter have Lewis-negative erythrocytes but saliva alpha1-4FucT activity. The genuine Lewis-negative individuals had mutations on both FUT3 alleles. In 66 healthy individuals, a gene dosage effect was detected as FUT3 heterozygous individuals had a lower alpha1-4FucT activity in saliva than did homozygous wild-type individuals. The lower enzyme level in heterozygous individuals resulted in a significantly (p <0.04) lower level of circulating sialyl-Lewis a structure in serum. This has the clinical impact that cut-off levels in tumor marker assays should be defined on the basis of genotyping. In the group of non-genuine Lewis-negative cancer patients, whose erythrocytes convert from Lewis-positive to Lewis-negative during the disease, FUT3 heterozygosity was significantly (p <0.05) more common.",
keywords = "ABO Blood-Group System, Alleles, Animals, Antigens, Tumor-Associated, Carbohydrate, Base Sequence, Blotting, Northern, COS Cells, Erythrocytes, Flow Cytometry, Fucosyltransferases, Humans, Lewis Blood-Group System, Molecular Sequence Data, Mutagenesis, Oligosaccharides, Phenotype, Polymerase Chain Reaction, Rats, Rats, Inbred Lew, Saliva, Transfection",
author = "Orntoft, {T F} and Vestergaard, {E M} and Esbern Holmes and Jakobsen, {J S} and N Grunnet and M Mortensen and P Johnson and P Bross and N Gregersen and Andresen, {Kirsten Skorstengaard} and Jensen, {Uffe Birk} and L Bolund and H Wolf",
year = "1996",
month = dec,
day = "13",
language = "English",
volume = "271",
pages = "32260--8",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "50",

}

RIS

TY - JOUR

T1 - Influence of Lewis alpha1-3/4-L-fucosyltransferase (FUT3) gene mutations on enzyme activity, erythrocyte phenotyping, and circulating tumor marker sialyl-Lewis a levels

AU - Orntoft, T F

AU - Vestergaard, E M

AU - Holmes, Esbern

AU - Jakobsen, J S

AU - Grunnet, N

AU - Mortensen, M

AU - Johnson, P

AU - Bross, P

AU - Gregersen, N

AU - Andresen, Kirsten Skorstengaard

AU - Jensen, Uffe Birk

AU - Bolund, L

AU - Wolf, H

PY - 1996/12/13

Y1 - 1996/12/13

N2 - Fucosylated glycoproteins carrying alpha1-4 fucose residues are of importance for cell adhesion and as tumor markers. The Lewis gene, FUT3, encodes the only known alpha1-4-fucosyltransferase (FucT), and individuals who are deficient in this enzyme type as Lewis-negative on erythrocytes. We examined the mutational spectrum of the Lewis gene in Denmark and found 6 different mutations. Five, T59G, T202C, C314T, G508A, and T1067A, were frequent, and one, C445A, was only detected in one out of 40 individuals. Allele-specific polymerase chain reaction as well as cloning of FUT3 alleles showed that the 202 and 314 mutations were co-located on the same allele. COS7 cells transfected with an allele having the 202/314 mutations lacked enzyme activity. Polymerase chain reaction-cleavage assays were established for the genotyping of healthy individuals as well as 20 genuine Lewis-negative cancer patients and 10 non-genuine. The latter have Lewis-negative erythrocytes but saliva alpha1-4FucT activity. The genuine Lewis-negative individuals had mutations on both FUT3 alleles. In 66 healthy individuals, a gene dosage effect was detected as FUT3 heterozygous individuals had a lower alpha1-4FucT activity in saliva than did homozygous wild-type individuals. The lower enzyme level in heterozygous individuals resulted in a significantly (p <0.04) lower level of circulating sialyl-Lewis a structure in serum. This has the clinical impact that cut-off levels in tumor marker assays should be defined on the basis of genotyping. In the group of non-genuine Lewis-negative cancer patients, whose erythrocytes convert from Lewis-positive to Lewis-negative during the disease, FUT3 heterozygosity was significantly (p <0.05) more common.

AB - Fucosylated glycoproteins carrying alpha1-4 fucose residues are of importance for cell adhesion and as tumor markers. The Lewis gene, FUT3, encodes the only known alpha1-4-fucosyltransferase (FucT), and individuals who are deficient in this enzyme type as Lewis-negative on erythrocytes. We examined the mutational spectrum of the Lewis gene in Denmark and found 6 different mutations. Five, T59G, T202C, C314T, G508A, and T1067A, were frequent, and one, C445A, was only detected in one out of 40 individuals. Allele-specific polymerase chain reaction as well as cloning of FUT3 alleles showed that the 202 and 314 mutations were co-located on the same allele. COS7 cells transfected with an allele having the 202/314 mutations lacked enzyme activity. Polymerase chain reaction-cleavage assays were established for the genotyping of healthy individuals as well as 20 genuine Lewis-negative cancer patients and 10 non-genuine. The latter have Lewis-negative erythrocytes but saliva alpha1-4FucT activity. The genuine Lewis-negative individuals had mutations on both FUT3 alleles. In 66 healthy individuals, a gene dosage effect was detected as FUT3 heterozygous individuals had a lower alpha1-4FucT activity in saliva than did homozygous wild-type individuals. The lower enzyme level in heterozygous individuals resulted in a significantly (p <0.04) lower level of circulating sialyl-Lewis a structure in serum. This has the clinical impact that cut-off levels in tumor marker assays should be defined on the basis of genotyping. In the group of non-genuine Lewis-negative cancer patients, whose erythrocytes convert from Lewis-positive to Lewis-negative during the disease, FUT3 heterozygosity was significantly (p <0.05) more common.

KW - ABO Blood-Group System

KW - Alleles

KW - Animals

KW - Antigens, Tumor-Associated, Carbohydrate

KW - Base Sequence

KW - Blotting, Northern

KW - COS Cells

KW - Erythrocytes

KW - Flow Cytometry

KW - Fucosyltransferases

KW - Humans

KW - Lewis Blood-Group System

KW - Molecular Sequence Data

KW - Mutagenesis

KW - Oligosaccharides

KW - Phenotype

KW - Polymerase Chain Reaction

KW - Rats

KW - Rats, Inbred Lew

KW - Saliva

KW - Transfection

M3 - Journal article

C2 - 8943285

VL - 271

SP - 32260

EP - 32268

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 50

ER -