Comparative genomic hybridization study of arsenic-exposed and non-arsenic-exposed urinary transitional cell carcinoma.
To compare the differences in DNA aberrations between arsenic-exposed and non-arsenic-exposed transitional cell carcinoma (TCC), we analyzed 19 arsenic-exposed and 29 non-arsenic-exposed urinary TCCs from Chi-Mei Hospital using comparative genomic hybridization. DNA aberrations were detected in 42 TCCs including 19 arsenic-exposed and 23 non-arsenic-exposed TCCs. Arsenic-exposed TCCs had more changes than unexposed TCCs (mean+/-SD, 6.6+/-2.9 vs. 2.9+/-2.2). Arsenic exposure was significantly associated with the number of DNA aberrations after adjustment for tumor stage, tumor grade and cigarette smoking in multiple regression analysis. The most frequent DNA gains, which were strikingly different between arsenic-exposed and non-arsenic-exposed TCCs, included those at 1p, 4p, 4q and 8q. A much higher frequency of DNA losses in arsenic-exposed TCCs compared with non-arsenic-exposed TCCs was observed in 10q, 11p and 17p. Chromosomal loss in 17p13 was associated not only with arsenic exposure, but also with tumor stage and grade. The p53 immunohistochemistry staining showed that chromosome 17p13 loss was associated with either p53 no expression (25%) or p53 overexpression (75%). The findings suggest that long-term arsenic exposure may increase the chromosome abnormality in TCC, and 17p loss plays an important role in arsenic-induced urinary carcinogenesis.
Hsu
Ling-I
LI
The Genomics Research Center, Academia Sinica, Taipei, Taiwan.
Chiu
Allen W
AW
Pu
Yeong-Shiau
YS
Wang
Yuan-Hung
YH
Huan
Steven K
SK
Hsiao
Cheng-Hsiang
CH
Hsieh
Fang-I
FI
Chen
Chien-Jen
CJ
D000328:Adult; D001151:Arsenic / Q000633:toxicity*; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D002869:Chromosome Aberrations / Q000187:drug effects; D002886:Chromosomes, Human, Pair 17 / Q000187:drug effects / Q000235:genetics; D004247:DNA / Q000187:drug effects / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D006824:Hybridization, Genetic; D007150:Immunohistochemistry; D008297:Male; D011042:Poisons / Q000633:toxicity*; D012044:Regression Analysis; D012907:Smoking / Q000473:pathology; D013624:Taiwan; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D014881:Water Supply / Q000032:analysis
D011042:Poisons; D004247:DNA; D001151:Arsenic