Carcinomas of the renal pelvis associated with smoking and phenacetin abuse:p53 mutations and polymorphism of carcinogen-metabolising enzymes

Bringuier, Pierre‐Paul; McCredie, Margaret; Sauter, Guido; Bilous, Michael; Stewart, John H.; Mihatsch, Michael J.; Kleihues, Paul; Ohgaki, Hideaki

doi:10.1002/(sici)1097-0215(19981023)79:5<531::aid-ijc15>3.0.co;2-4

Cited by 26 publications

(4 citation statements)

References 28 publications

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“…In the present study, urothelial hyperplasia in the renal papillae was shown to be an age-dependent pathological feature in the kidneys of BN rats. In clinically, hyperplasia of the urothelium has been reported in humans treated with phenacetin, which is an analgesic drug that shows adverse effects during urothelial carcinoma [2]. However, no malignant findings were observed in the present study, and the clinical significance of this urothelial lesion in the BN rats remained unclear.…”

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confidence: 51%

Age-Related Histological Changes in Kidneys of Brown Norway Rat

Yabuki

Yoneshige

Tanaka

et al. 2014

The Journal of Veterinary Medical Science

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In this study, age-dependent histological changes in the kidneys of Brown Norway rat, a strain useful for conducting aging research, were evaluated. Examination was performed at 3, 12, 18, 24 and 30 months of age. Sclerotic and hypertrophic changes of the glomeruli were observed, and quantitative scores of these changes persistently increased with age. A marginal increase in scores was observed for glomerular cystic changes and tubulointerstitial damage. Further, urothelial hyperplasia was observed in the renal papillae, particularly at 30 months of age. In conclusion, the findings of the present study demonstrate that the Brown Norway strain exhibits persistent, but mild progression of age-dependent renal histological changes.

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confidence: 51%

Age-Related Histological Changes in Kidneys of Brown Norway Rat

Yabuki

Yoneshige

Tanaka

et al. 2014

The Journal of Veterinary Medical Science

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“…Driver genes mutated in a large fraction of UTUCs include previously implicated genes [ HRAS (33), TP53 (34), and FGFR3 (35)] and genes not previously reported to be mutated in UTUCs ( MLL2 , CREBBP , STAG2 , BRCA2 , KDM6A , and NRAS ). Of the newly identified genes, several that were mutated in a high fraction of UTUCs ( MLL2 , CREBBP , and KDM6A ) were of particular interest because they implicate defects in chromatin modification in the development of UTUCs.…”

Section: Discussionmentioning

confidence: 99%

Mutational Signature of Aristolochic Acid Exposure as Revealed by Whole-Exome Sequencing

et al. 2013

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In humans, exposure to aristolochic acid (AA) is associated with urothelial carcinoma of the upper urinary tract (UTUC). Exome sequencing of UTUCs from 19 individuals with documented exposure to AA revealed a remarkably large number of somatic mutations and an unusual mutational signature attributable to AA. Most of the mutations (72%) in these tumors were A:T-to-T:A transversions, located predominantly on the nontranscribed strand, with a strong preference for deoxyadenosine in a consensus sequence (T/CAG). This trinucleotide motif overlaps the canonical splice acceptor site, possibly accounting for the excess of splice site mutations observed in these tumors. The AA mutational fingerprint was found frequently in oncogenes and tumor suppressor genes in AA-associated UTUC. The AA mutational signature was observed in one patient’s tumor from a UTUC cohort without previous indication of AA exposure. Together, these results directly link an established environmental mutagen to cancer through genome-wide sequencing and highlight its power to reveal individual exposure to carcinogens.

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“…It is reported that toxic agents in the urine can transform urothelial cells and induce tumorigenesis [7] . A small percentage of UC arises following exposure to toxic chemicals including aristolochic acid, and abuse of the drug phenacetin [8] , [9] . However, the most important risk factor for urothelial cancer is cigarette smoking [10] .…”

Section: Introductionmentioning

confidence: 99%