LOSS OF ABH ANTIGEN EXPRESSION IN BLADDER-CANCER IS NOT CAUSED BY LOSS OF HETEROZYGOSITY OF THE ABO LOCUS

The significance of loss of heterozygosity (LOH) of chromosome 9 as an early event in human bladder tumors has been demonstrated by several studies. We have studied LOH of the ABO gene locus at 9q34.2 by means of polymerase chain reaction (PCR) genotyping of tumor preparations an d leukocytes. Twenty-two tumors, all of which were immunohistochemical ly negative for ABH antigens, were examined. Eleven tumors were from b lood-group O individuals, and were examined by denaturing gradient gel electrophoresis (DGGE). They showed normal band patterns with no sign of single base mutations or LOH. All II A and B tumors were sorted on a fluorescence-activated cell sorter (FACS) according to DNA content, thereby making it possible to study differences in genotype between s ubpopulations of cells in the same tumor. In 2 genotypically AO cases, we found 2 aneuploid subpopulations. In both cases, the most abnormal , with the highest DNA content, showed complete loss of the O allele, leaving the A allele intact. As all tumors were ABH antigen-negative, this study demonstrates that LOH of the ABO locus on chromosome 9q34 i s not the cause of loss of blood-group ABH expression in human bladder cancer. (C) 1995 Wiley-Liss, Inc.