Arylamine N-acetyltransferase type 2 (NAT2), chromosome 8 aneuploidy, and identification of a novel NATI cosmid clone: An investigation in bladder cancer by interphase FISH

Two genes (arylamine N-acetyltransferase types 1 and 2, NAT1 and NAR2), whi ch are known to metabolize bladder carcinogens, are located on chromosome b and 8p22. Alterations in chromosome 8, including deletions of 8p, occur fre quently in many epithelium-derived tumors. In this study, fluorescence in s itu hybridization (FISH) was used for study of the relationship between chr omosome 8 deletions in the region of NAT1 and NAT2 and grade and stage of t umor in bladder cancer. Cells from 52 bladder tumors were examined by dual- labeling FISH with a centromere 8-specific probe and a cosmid probe for NAT 2. A more limited number were examined for loss with both the NAT2 probe an d a newly constructed NAT1 -specific cosmid. Loss of NAT2 was found in 6/52 patients in more than 30% of cells, and in 10/52 in 10%-30% of cells exami ned. Six samples also showed loss of NAT1, indicating that the region of de letion spans at least the distance of the two genes. No obvious correlation between loss of NAT genes with grade and stage of tumor was evident. Inter estingly, 17/52 (32%) tumors showed an increased copy number of chromosome 8, with tumors of low stage showing relatively smaller increases of chromos ome 8. Loss of 8p22 and genetic instability involving chromosome 8 indicate that this chromosome is important in bladder cancer and that NAT genes wil l act as important genetic landmarks in defining deletions in this disease. Genes Chromosomes Cancer 25:376-383, 1999. (C) 1999 Wiley-Liss, Inc.