Pinto-Leite Rosário, Carreira Isabel, Melo Joana, Ferreira Susana Isabel, Ribeiro Ilda, Ferreira Jaqueline, Filipe Marco, Bernardo Carina, Arantes-Rodrigues Regina, Oliveira Paula, Santos Lúcio
Cytogenetic Laboratory, Department of Human Genetics, Hospital Center of Trás-os-Montes and Alto Douro, Vila Real, Portugal.
Tumour Biol. 2014 May;35(5):4599-617. doi: 10.1007/s13277-013-1604-3. Epub 2014 Jan 24.
Several genomic regions are frequently altered and associated with the type, stage and progression of urinary bladder cancer (UBC). We present the characterization of 5637, T24 and HT1376 UBC cell lines by karyotyping, fluorescence in situ hybridization (FISH), array comparative genomic hybridization (aCGH) and multiplex ligation-dependent probe amplification (MLPA) analysis. Some cytogenetic anomalies present in UBC were found in the three cell lines, such as chromosome 20 aneuploidy and the loss of 9p21. Some gene loci losses (e.g. CDKN2A) and gains (e.g. HRAS, BCL2L1 and PTPN1) were coincident across all cell lines. Although some significant heterogeneity and complexity were detected between them, their genomic profiles exhibited a similar pattern to UBC. We suggest that 5637 and HT1376 represent the E2F3/RB1 pathway due to amplification of 6p22.3, concomitant with loss of one copy of RB1 and mutation of the remaining copy. The HT1376 presented a 10q deletion involving PTEN region and no alteration of PIK3CA region which, in combination with the inactivation of TP53, bears more invasive and metastatic properties than 5637. The T24 belongs to the alternative pathway of FGFR3/CCND1 by presenting mutated HRAS and over-represented CCND1. These cell lines cover the more frequent subtypes of UBC and are reliable models that can be used, as a group, in preclinical studies.
几个基因组区域经常发生改变，并与膀胱癌（UBC）的类型、分期和进展相关。我们通过核型分析、荧光原位杂交（FISH）、阵列比较基因组杂交（aCGH）和多重连接依赖探针扩增（MLPA）分析对5637、T24和HT1376膀胱癌细胞系进行了特征描述。在这三种细胞系中发现了一些存在于膀胱癌中的细胞遗传学异常，如20号染色体非整倍体和9p21缺失。一些基因位点的缺失（如CDKN2A）和增加（如HRAS、BCL2L1和PTPN1）在所有细胞系中都是一致的。尽管在它们之间检测到了一些显著的异质性和复杂性，但它们的基因组图谱与膀胱癌呈现出相似的模式。我们认为，由于6p22.3扩增，同时伴有RB1一个拷贝的缺失和另一个拷贝的突变，5637和HT1376代表E2F3/RB1途径。HT1376存在涉及PTEN区域的10q缺失，且PIK3CA区域无改变，与TP53失活相结合，其侵袭性和转移性比5637更强。T24通过呈现突变的HRAS和过表达的CCND1属于FGFR3/CCND1的替代途径。这些细胞系涵盖了膀胱癌中较常见的亚型，是一组可用于临床前研究的可靠模型。
