Zheng Min, Simon Ronald, Mirlacher Martina, Maurer Robert, Gasser Thomas, Forster Thomas, Diener Pierre Andre, Mihatsch Michael J, Sauter Guido, Schraml Peter
Institute of Pathology, University of Basel, Schoenbeinstrasse 40, CH-4031 Basel, Switzerland.
Am J Pathol. 2004 Jul;165(1):63-9. doi: 10.1016/S0002-9440(10)63275-0.
Studies by comparative genome hybridization have suggested that 5p amplification is related to tumor progression in urinary bladder cancer. In this study seven genes (TAS2R, ADCY2, DNAH5, CTNND2, TRIO, ANKH, and MYO10) located to 5p15.31-5p15.1 were analyzed by fluorescence in situ hybridization using a tissue microarray containing samples from tumors and cell lines with known 5p amplification by comparative genome hybridization. Amplification frequency was highest for TRIO, which maps to 5p15.2 and encodes a protein with a putative role in cell-cycle regulation. To further investigate the role of TRIO amplification in bladder cancer, a tissue microarray containing samples from 2317 bladder tumors was used for fluorescence in situ hybridization analysis. TRIO amplification was strongly associated with invasive tumor phenotype, high tumor grade, and rapid tumor cell proliferation (Ki67 LI) (P < 0.0001 each). Only 7 of 456 pTaG1/G2 tumors (1.5%) but 62 of 485 pT1-4 carcinomas (12.8%) had TRIO amplification. TRIO amplification was not associated with poor prognosis. Using a frozen bladder tumor tissue microarray RNA in situ hybridization confirmed that TRIO is up-regulated in amplified tumors. It is concluded that TRIO up-regulation through amplification has a potential role in bladder cancer progression.
比较基因组杂交研究表明，5p扩增与膀胱癌的肿瘤进展相关。在本研究中，通过荧光原位杂交分析了位于5p15.31 - 5p15.1的7个基因（TAS2R、ADCY2、DNAH5、CTNND2、TRIO、ANKH和MYO10），所用组织微阵列包含来自肿瘤和细胞系的样本，这些样本通过比较基因组杂交已知存在5p扩增。TRIO的扩增频率最高，它定位于5p15.2，编码一种在细胞周期调控中可能起作用的蛋白质。为了进一步研究TRIO扩增在膀胱癌中的作用，使用了一个包含2317例膀胱肿瘤样本的组织微阵列进行荧光原位杂交分析。TRIO扩增与侵袭性肿瘤表型、高肿瘤分级和快速肿瘤细胞增殖（Ki67 LI）密切相关（每项P < 0.0001）。456例pTaG1/G2肿瘤中只有7例（1.5%）有TRIO扩增，但485例pT1 - 4癌中有62例（12.8%）有TRIO扩增。TRIO扩增与预后不良无关。使用冷冻膀胱肿瘤组织微阵列RNA原位杂交证实，TRIO在扩增的肿瘤中上调。结论是，通过扩增导致的TRIO上调在膀胱癌进展中具有潜在作用。
