Characterization of 17.94, a novel anaplastic Wilms' tumor cell line
Characterization of 17.94, a novel anaplastic Wilms' tumor cell line
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DOI：
10.1016/j.cancergen.2012.04.009
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发表时间：
2012-06-01
期刊：
影响因子：
1.9
通讯作者：
Malik, Karim
中科院分区：
文献类型：
--
作者：
Brown, Keith W.;Charles, Adrian;Malik, Karim
尽管在理解肾母细胞瘤（WT）的分子发病机制方面取得了相当大的进展，但其细胞生物学尚不清楚，部分原因是缺乏已建立的WT细胞系。我们在这里报告建立了一个新的间变性WT细胞系，17.94，表达NCAM，SALL 1和CITED 1-表型特征预期的后肾胚细胞衍生的细胞。用12-O-十四酰基佛波醇13-乙酸酯处理17.94细胞引起形态学变化，这导致NCAM和SALL 1表达降低，但波形蛋白的表达得以维持，表明基质分化的潜力。17.94细胞系含有TP 53突变，与原始肿瘤的间变性组织学一致，但缺乏WT 1、WTX或CTNNB 1突变，这些突变是WT发病机制中涉及的其他基因。17.94细胞在7 p、11 p或16 q处未显示杂合性丢失;然而，在几个位点检测到DNA超甲基化，包括H19差异甲基化区域（指示11 p15处IGF 2印迹的丢失）和5 q31处的PCDH@基因簇。17.94细胞系的产生将有助于进一步剖析WT发病机制中的遗传-表观遗传相互作用。
Despite considerable advances in understanding the molecular pathogenesis of Wilms' tumor (WT), its cell biology is less well understood, partly due to the paucity of established WT cell lines. We report here the establishment of a new anaplastic WT cell line, 17.94, which expressed NCAM, SALL1, and CITED1-phenotypic features expected of metanephric blastema-derived cells. Treatment of 17.94 cells with 12-O-Tetradecanoylphorbol 13-acetate caused morphological changes, which led to reduced NCAM and SALL1 expression, but expression of vimentin was maintained, indicating a potential for stromal differentiation. The 17.94 cell line contained a TP53 mutation, consistent with the anaplastic histology of the original tumor, but lacked mutations in WT1, WTX, or CTNNB1, which are the other genes involved in WT pathogenesis. The 17.94 cells showed no loss of heterozygosity at 7p, 11p, or 16q; however, DNA hypermethylation was detected at several loci, including the H19 differentially methylated region (indicative of loss of imprinting of IGF2 at 11p15) and at the PCDH@ gene clusters at 5q31. The derivation of the 17.94 cell line should help to further dissect the genetic-epigenetic interactions involved in the pathogenesis of WT.