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Short telomeres and chromosome instability prior to histologic malignant progression and cytogenetic aneuploidy in papillary urothelial neoplasms.

cancer

FISH (Fluorescent In Situ Hybridization)

genetics

telomere length

Authors: Naotaka N. Izumiyama-Shimomura, Ken-Ichi K. Nakamura, Junko J. Aida, Naoshi N. Ishikawa, Mie M. Kuroiwa, Naoki N. Hiraishi, Mutsunori M. Fujiwara, Yuichi Y. Ishikawa, Naoko N. Inoshita, Junji J. Yonese, Masaaki M. Matsuura, Steven S S SS. Poon, Tomio T. Arai, Kaiyo K. Takubo
Published: 03/17/2013, Urologic oncology

Purpose

Evaluation of the relationships existing among 3 histologic types of urothelial tumors, chromosomal instability, and telomere length.

Patients And Methods

We examined 37 consecutive cases of papillary urothelial neoplasm, from which 26 (70.3%) were suitable for karyotype analysis, comprising 7 papillary urothelial neoplasms of low malignant potential (PUNLMPs), 10 low-grade papillary urothelial carcinomas (PUCs), and 9 high-grade PUCs. We performed karyotype and anaphase bridge analyses, and measured telomere lengths by quantitative fluorescence in situ hybridization.

Results

PUNLMPs were always diploid and had anaphase bridges. Low-grade PUCs showed diploidy (n = 2), hypoploidy (n = 4) and polyploidy (n = 4), and high-grade PUCs showed diploidy (n = 1) and polyploidy (n = 8); both had anaphase bridges. The incidence of anaphase bridges did not differ significantly between PUNLMPs and high-grade PUCs (P = 0.105). The telomere lengths of PUNLMP, low-grade PUC, and high-grade PUC, expressed as mean telomere fluorescence units (TFU) ± SD, were 7906 ± 3197, 4893 ± 1567, and 3299 ± 1406, respectively. The differences among the 3 groups were significant. However, 42.9% of the PUNLMPs had shorter telomeres than the mean value for low-grade PUCs, and 30.0% of the low-grade PUCs had shorter telomeres than those for high-grade PUCs. There was an inverse correlation between telomere length and the incidence of anaphase bridges.

Conclusions

PUNLMP appears to progress to low-grade PUC and high-grade PUC in association with telomere shortening and chromosomal instability. Our data suggest that critically shortened telomeres cause chromosomal instability during progression of papillary urothelial neoplasms.

Copyright © 2014 Elsevier Inc. All rights reserved.
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