Genetic and epigenetic alterations of the blood group ABO gene in oral squamous cell carcinoma
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Genetic and epigenetic alterations of the blood group ABO gene in oral squamous cell carcinoma. / Gao, Shan; Worm, Jesper; Guldberg, Per; Eiberg, Hans; Krogdahl, Annelise; Liu, Chung-Ji; Reibel, Jesper; Dabelsteen, Erik.
In: International journal of cancer. Journal international du cancer, Vol. 109, No. 2, 20.03.2004, p. 230-7.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Genetic and epigenetic alterations of the blood group ABO gene in oral squamous cell carcinoma
AU - Gao, Shan
AU - Worm, Jesper
AU - Guldberg, Per
AU - Eiberg, Hans
AU - Krogdahl, Annelise
AU - Liu, Chung-Ji
AU - Reibel, Jesper
AU - Dabelsteen, Erik
N1 - Copyright 2003 Wiley-Liss, Inc.
PY - 2004/3/20
Y1 - 2004/3/20
N2 - Loss of histo-blood group A and B antigen expression is a frequent event in oral carcinomas and is associated with decreased activity of glycosyltransferases encoded by the ABO gene. We examined 30 oral squamous cell carcinomas for expression of A and B antigens and glycosyltransferases. We also examined DNA from these tumors for loss of heterozygosity (LOH) at markers surrounding the ABO locus at chromosome 9q34, for loss of specific ABO alleles, and for hypermethylation of the ABO promoters. Loss of A or B antigen expression was found in 21 of 25 tumors (84%) and was a consistent feature of tumors lacking expression of A/B glycosyltransferases. LOH at 9q34 was found in 7 of 27 cases (26%), and one case showed microsatellite instability. Among 20 AO/BO cases, 3 showed loss of the A/B allele and 3 showed loss of the O allele. Analysis of the proximal ABO promoter by methylation-specific PCR and melting curve analysis showed hypermethylation in 10 of 30 tumors (33.3%), which was associated with loss of A/B antigen expression. ABO promoter hypermethylation was also found in hyperplastic or dysplastic tissues adjacent to the tumors, suggesting that it is an early event in tumorigenesis. Collectively, we have identified molecular events that may account for loss of A/B antigen expression in 67% of oral squamous cell carcinomas.
AB - Loss of histo-blood group A and B antigen expression is a frequent event in oral carcinomas and is associated with decreased activity of glycosyltransferases encoded by the ABO gene. We examined 30 oral squamous cell carcinomas for expression of A and B antigens and glycosyltransferases. We also examined DNA from these tumors for loss of heterozygosity (LOH) at markers surrounding the ABO locus at chromosome 9q34, for loss of specific ABO alleles, and for hypermethylation of the ABO promoters. Loss of A or B antigen expression was found in 21 of 25 tumors (84%) and was a consistent feature of tumors lacking expression of A/B glycosyltransferases. LOH at 9q34 was found in 7 of 27 cases (26%), and one case showed microsatellite instability. Among 20 AO/BO cases, 3 showed loss of the A/B allele and 3 showed loss of the O allele. Analysis of the proximal ABO promoter by methylation-specific PCR and melting curve analysis showed hypermethylation in 10 of 30 tumors (33.3%), which was associated with loss of A/B antigen expression. ABO promoter hypermethylation was also found in hyperplastic or dysplastic tissues adjacent to the tumors, suggesting that it is an early event in tumorigenesis. Collectively, we have identified molecular events that may account for loss of A/B antigen expression in 67% of oral squamous cell carcinomas.
KW - ABO Blood-Group System
KW - Adult
KW - Aged
KW - Carcinoma, Squamous Cell
KW - DNA Methylation
KW - DNA, Neoplasm
KW - Female
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Loss of Heterozygosity
KW - Male
KW - Middle Aged
KW - Mouth Neoplasms
KW - Promoter Regions, Genetic
U2 - 10.1002/ijc.11592
DO - 10.1002/ijc.11592
M3 - Journal article
C2 - 14750174
VL - 109
SP - 230
EP - 237
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 2
ER -
ID: 119538605