Identification of Early p53 Mutations in Clam Ileocystoplasties Using Restriction Site Mutation Assay

Ivil, Kenneth D.; Jenkins, S. A.; Doak, Shareen H.; Hawizy, Azad; Kynaston, Howard; Parry, Elizabeth M.; Jenkins, Gareth; Parry, James M.; Stephenson, T. P.

doi:10.1016/j.urology.2007.06.1121

Cited by 9 publications

(6 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, recent studies using fluorescent in situ hybridization (FISH) and restriction site mutation (RSM) techniques reported aneuploidy of chromosomes 8, 9 and 18 9 and early p53 mutations 10 in perianastomotic tissue obtained from augmentation cystoplasty patients. Therefore, the results of these studies suggest that the mucosa close to the enterovesical anastomosis may be more genetically unstable than that distant from the suture line.…”

Section: Discussionmentioning

confidence: 87%

Comparative genomic hybridization (CGH) of augmentation cystoplasties

et al. 2007

View full text Add to dashboard Cite

Objective: Tumors arising within augmentation cystoplasties are aggressive, have poor prognosis and the majority are not detected at follow-up cystoscopy. Genetic changes in tumors precede morphological abnormalities. Therefore, the aim of this study was to investigate whether genetic abnormalities detected by comparative genomic hybridization (CGH) could be used to identify those patients with augmentation cystoplasties at increased risk of tumorigenesis. Methods: Bladder biopsy samples were obtained from 16 augmentation cystoplasty patients both distant from and near to the enterovesical anastomosis. CGH was used to detect genetic abnormalities in DNA extracted from the biopsies, archival specimens of two augmentation cystoplasties and two de novo bladder adenocarcinomas. Results: A greater number of amplifications on 2p, 3q, 8q, 9p, 17p, 18pq and 20pq, were observed in bladder biopsies obtained near to the enterovesical anastomosis compared to those taken distant to the suture line. CGH of archival augmentation cystoplasty tumor DNA indicated abnormalities at several loci with amplifications at 2q, 5q, 10p and 21pq, while deletions occurred at 5p and 16p. Conclusions: The results of this study suggest that the urothelium adjacent to the bladder and/or bowel anastomosis in augmentation cystoplasties is genetically unstable. Furthermore, longitudinal studies are required to establish whether or not patients exhibiting genetic instability following augmentation cystoplasty are at greater risk of developing tumors than those with genetically stable epithelia.

show abstract

Section: Discussionmentioning

confidence: 87%

Comparative genomic hybridization (CGH) of augmentation cystoplasties

et al. 2007

View full text Add to dashboard Cite

show abstract

“…As depicted in the model in Figure 7, gastrointestinal tissues placed into this environment lack such robust protective mechanisms and thus may sustain greater osmotic stress from urinary solutes, disrupting normal cellular processes such as the repair of DNA damage and leading to mutagenesis. Accumulation of mutations has been identified in these tissues [8], suggesting that susceptibility to mutations may underlie their risk of malignant transformation. Cells from the gastrointestinal tract also exhibit a higher index of mitosis than that of transitional epithelium [42], and in the bladder microenvironment greater DNA replication in the face of suppressed damage recognition and repair may pose an added risk of mutagenesis and resultant carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…Experimental animal data [4–6] and surveillance biopsy data in humans [7] demonstrate that transitional metaplasia is frequently observed in the gastrointestinal segment of bladder augmentations, and this metaplasia may herald the onset of more severe dysplasia and malignancy. Recent analyses of biopsied enterovesicular anastomoses revealed mutations in p53 by restriction site mutation assay in 20% of patients, but found no mutations in the native bladder tissue [8], suggesting a tissue-specific response to the bladder microenvironment. The mechanism underlying the increased metaplasia, dysplasia, and malignancy of augmented bladders has been hypothesized to be due to microenvironmental factors including chronic bacterial colonization with the subsequent formation of nitrosamines, extremes of urinary pH, chronic trauma from urolithiasis, and the apposition of dissimilar tissues.…”

Section: Introductionmentioning

confidence: 99%

Increased cancer risk of augmentation cystoplasty: Possible role for hyperosmolal microenvironment on DNA damage recognition

Dixon¹,

Chu²,

Henry³

et al. 2009

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

View full text Add to dashboard Cite

Patients who have had surgical bladder augmentation have an increased risk of bladder malignancy, though the mechanism for this increased risk is unknown. Hyperosmolal microenvironments such as the bladder may impair DNA damage signaling and repair; this effect may be more pronounced in tissues not normally exposed to such conditions. Comparing gastric and colon epithelial cell lines to transitional epithelial cell lines gradually adapted to an osmolality of 600mOsm/kg with either sodium chloride or urea, cell lines of gastrointestinal origin were inhibited in their ability to activate ATM and downstream effectors of DNA damage signaling and repair such as p53, Nbs1, replication protein A (RPA), and γH2AX following the induction of DNA damage with etoposide. In contrast, bladder cell lines demonstrated a preserved ability to phosphorylate ATM and its effectors under conditions of hyperosmolal urea, and to a lesser extent with sodium chloride. The bladder cell lines' ability to respond to DNA damage under hyperosmolal conditions may be due in part to protective mechanisms such as the accumulation of intracellular organic osmolytes and the uroplakincontaining asymmetric unit membrane as found in transitional epithelial cells, but not in gastrointestinal cells. Failure of such protective adaptations in the tissues used for augmentation cystoplasties may place these tissues at increased risk for malignancy.

show abstract

“… 6 Furthermore, a variety of gene aberrations have been found in the region of enterovesical anastomosis in patients treated with ileocystoplasty, such as chromosomal numerical abnormalities in chromosomes 18, 9, and 8, 7 and p53 mutations. 8 These findings suggest that multiple factors are involved in the bladder carcinogenesis after cystoplasty.…”

Section: Discussionmentioning

confidence: 92%

Adenoma-carcinoma Sequence in the Bladder After Augmentation Cystoplasty

Naito

Kawai

Fujimura

et al. 2014

Urology Case Reports

View full text Add to dashboard Cite

We present a case of a 64-year-old woman showing multistep progression from adenoma to adenocarcinoma in the bladder 46 years after augmentation ileocystoplasty. She underwent augmentation ileocystoplasty for tuberculous contracted bladder at 18 years. After 44 years, tubulovillous adenomas were found and resected at the ileovesical anastomosis site. After 2 more years, bladder tumors recurred and revealed adenocarcinomas. Finally, radical cystectomy was required because of frequent recurrence and tumor extensiveness. To our knowledge, this is the first case demonstrating adenoma-carcinoma sequence histopathologically in the bladder after augmentation cystoplasty, indicating multistep carcinogenesis similar to intestinal carcinogenesis.

show abstract

Identification of Early p53 Mutations in Clam Ileocystoplasties Using Restriction Site Mutation Assay

Cited by 9 publications

References 19 publications

Comparative genomic hybridization (CGH) of augmentation cystoplasties

Comparative genomic hybridization (CGH) of augmentation cystoplasties

Increased cancer risk of augmentation cystoplasty: Possible role for hyperosmolal microenvironment on DNA damage recognition

Adenoma-carcinoma Sequence in the Bladder After Augmentation Cystoplasty

Contact Info

Product

Resources

About