Genetic aberrations of NAT2 and chromosome 8: their association with progression in transitional cell carcinoma of the urinary bladder.
OBJECTIVE
N-acetyltransferase 2 (NAT2), mapped to 8p22, is a polymorphic enzyme which metabolizes aromatic amines. Loss of heterozygosity of 8p22 is associated with an increased risk of bladder cancer. This study evaluated NAT2 and chromosome 8 in sequential tumours from bladder cancer patients to determine if NAT2 alterations increase the risk of progression.


METHODS
Thirty-seven sequential carcinomas from 19 patients were assessed using fluorescence in situ hybridization.


RESULTS
Five carcinomas showed loss of NAT2; 4 of these were from pTa/pT1 tumours. Polysomy 8 was observed in 4 of 14 (29%) primary carcinomas (pTa/pT1), in 4 of 12 (33%) pTa/pT1 recurrences, and in 90% (9/10) of the detrusor muscle invasive tumours (pT2+). 6 of 8 (75%) locally invasive tumours with polysomy 8 were from patients who subsequently developed disease progression (pT2+). In total, 13.5% (5/37) of the carcinomas were abnormal for NAT2, and 46% (17/37) were abnormal for chromosome 8 copy number. Polysomy 8 was associated with high grade (p = 0.01) and stage (p = 0.03) and disease progression (p = 0.03).


CONCLUSIONS
Whilst there does not appear to be an association between loss of NAT2 and risk of progression in transitional cell carcinoma, the high rate of polysomy of chromosome 8 implies that other genes on this chromosome significantly influence disease progression.
Watters
A D
AD
Department of Surgery, Glasgow Royal Infirmary, University of Glasgow, Glasgow G31 2ER, UK. adw10q@clinmed.gla.ac.uk
Stacey
M W
MW
Going
J J
JJ
Grigor
K M
KM
Cooke
T G
TG
Sim
E
E
Bartlett
J M
JM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology*; D002869:Chromosome Aberrations; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*
D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human