Short telomeres and chromosome instability prior to histologic malignant progression and cytogenetic aneuploidy in papillary urothelial neoplasms
Short telomeres and chromosome instability prior to histologic malignant progression and cytogenetic aneuploidy in papillary urothelial neoplasms
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DOI：
10.1016/j.urolonc.2012.12.005
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发表时间：
2014-02-01
影响因子：
2.7
通讯作者：
Takubo, Kaiyo
中科院分区：
文献类型：
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作者：
Izumiyama-Shimomura, Naotaka;Nakamura, Ken-ichi;Takubo, Kaiyo
目的：探讨尿路上皮肿瘤三种组织学类型与染色体不稳定性、端粒长度之间的关系。患者和方法：我们连续检查了37例尿路上皮乳头状癌，其中26例(70.3%)适合进行核型分析，包括7例低度恶性潜能的乳头状尿路上皮肿瘤(PUNLMPs)，10例低度恶性的乳头状尿路上皮癌(PUC)，9例高度恶性的PUC。我们进行了核型分析和后期桥分析，并通过定量荧光原位杂交测量了端粒长度。结果：PUNLMP始终为二倍体，并有后期桥。低度恶性PUC有二倍体(n=2)、亚倍体(n=4)和多倍体(n=4)，高度恶性PUC有二倍体(n=1)和多倍体(n=8)，均有后期桥。晚期桥在PUNLMP和高级别PUC中的发生率差异无统计学意义(P=0.105)。以平均端粒荧光单位(TFU)+/-SD表示的PUNLMP、低度恶性PUC和高度恶性PUC的端粒长度分别为7906+/-3197、4893+/-1567和3299-1406。3组间差异有统计学意义。然而，42.9%的PUNLMP端粒长度低于低度恶性PUC的平均值，30.0%的低度恶性PUC端粒长度短于高度恶性PUC。端粒长度与后期桥的发生率呈负相关。结论：PUNLMP进展为低度恶性PUC和高度恶性PUC，与端粒缩短和染色体不稳定有关。我们的数据表明，在乳头状尿路上皮肿瘤的进展过程中，端粒的严重缩短会导致染色体的不稳定。(C)2014 Elsevier Inc.保留所有权利。
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), hypoptoidy (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. (C) 2014 Elsevier Inc. All rights reserved.