title: Loss of blood group A antigen expression in bladder cancer caused by allelic loss and/or methylation of the ABO gene.
abstract: Loss of ABO blood group antigen expression has been reported in transitional cell carcinoma (TCC) of the bladder. Synthesis of the ABO blood group antigen was genetically determined by allelic variants of the ABO gene assigned on 9q34.1. We analyzed loss of heterozygosity (LOH) and promoter hypermethylation of the ABO gene in TCC and compared them with alterations of A antigen expression in TCC, dysplasia and normal urothelium. A total of 81 samples of TCC of the bladder obtained from transurethral resection (TUR) (n=44) and radical cystectomy (n=37) were examined. Expression of the A antigen was evaluated by immunohistochemical staining (IHC) using anti-A antigen monoclonal antibody. LOH of the ABO gene locus was examined by blunt-end single-strand DNA conformational polymorphism (SSCP) analysis using flouresence-based auto sequencer. Promoter hypermethylation of the ABO gene were examined by bisulfite PCR-SSCP (BiPS) analysis and/or methylation-specific PCR (MSP). Loss of A allele and/or hypermethylation were significantly associated with abnormal expression of the A antigen in cases undergoing TUR (P=0.02) and radical cystectomy (P=0.0005). For the analysis of the concomitant dysplasia in 23 cases with TCC of the bladder, the expression of the A antigen was maintained, regardless of the A allelic loss or methylation status in the tumor. In conclusion, A allelic loss and hypermethylation in the promoter region of the ABO gene showed significant correlation with reduction of A antigen expression in TCC, while the expression of the A antigen is maintained in concomitant dysplasia or normal urothelium, suggesting that loss of the ABO gene and/or its promoter hypermethylation is a specific marker for TCC.
authors.affiliation: Oncogene Research Unit/Cancer Prevention Unit, Tochigi Cancer Center Research Institute, Tochigi 320-0834, Japan.
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Chihara
authors.forename: Kokichi
authors.initials: K
authors.lastname: Sugano
authors.forename: Ayumi
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nakazono
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujimoto
authors.forename: Tadao
authors.initials: T
authors.lastname: Kakizoe
authors.forename: Kiyohide
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Setsuo
authors.initials: S
authors.lastname: Hirohashi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hirao
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000097:blood / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D001749:Urinary Bladder Neoplasms / Q000097:blood / Q000235:genetics*
chemical_list: D000017:ABO Blood-Group System; D000951:Antigens, Neoplasm