Genes for human arylamine N-acetyltransferases in relation to loss of the short arm of chromosome 8 in bladder cancer

Polymorphisms of N-acetyltransferase type 2 (NAT2) conferring the slow acet ylator phenotype have been linked to increased susceptibility to arylamine- induced bladder cancer in Caucasians. Genes for NAT2, the other NAT isozyme , NAT1, and a NAT pseudogene (NATP) are found on 8p22, a region displaying loss of heterozygosity, particularly in invasive bladder tumours, A restric tion enzyme digestion map has defined the relative positions of the NAT gen es to each other and to adjacent CpG islands, NAT2, as a polymorphic gene o f known function, is a potentially valuable marker for the detection of los s of heterozygosity in 8p22, Two approaches to investigate loss of heterozy gosity at the NAT2 locus in bladder tumours have been used, (1) A cosmid co ntaining NAT2 has been used in fluorescence in-situ hybridization on human exfoliated bladder cells collected from unselected bladder cancer outpatien ts, Loss of signal from the NAT2 cosmid was found in nine of the 20 patient s, (2) A panel of 13 human bladder tumours was investigated for loss of het erozygosity using the polymorphism in the NAT2 gene as a marker, Loss of he terozygosity at the NAT2 locus has been compared with loss of heterozygosit y at adjacent microsatellite marker sites known to be located on 8p, There is agreement between loss of heterozygosity at the NAT2 locus and adjacent microsatellite marker loci in 11 of the tumours but two of the tumours appe ar to show retention at the NAT2 locus, More extensive mapping of the regio n around the NAT loci, particularly on the centromeric side, is important t o pinpoint possible tumour suppressor genes or their modifiers in the regio n, There are no other expressed sequences known in this region and therefor e NAT genes are important genetic landmarks, Pharmacogenetics 9:1-8 (C) 199 9 Lippincott Williams & Wilkins.