Brown Keith W, Charles Adrian, Dallosso Anthony, White Gillian, Charlet Jessica, Standen Graham R, Malik Karim
University of Bristol, School of Cellular & Molecular Medicine, United Kingdom.
Cancer Genet. 2012 Jun;205(6):319-26. doi: 10.1016/j.cancergen.2012.04.009.
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.
尽管在了解肾母细胞瘤（WT）的分子发病机制方面取得了相当大的进展，但其细胞生物学仍不太清楚，部分原因是缺乏成熟的WT细胞系。我们在此报告建立了一种新的间变性WT细胞系17.94，其表达神经细胞黏附分子（NCAM）、SALL1和CITED1，这些是后肾胚基来源细胞预期的表型特征。用12 - O - 十四烷酰佛波醇13 - 乙酸酯处理17.94细胞会导致形态变化，从而导致NCAM和SALL1表达降低，但波形蛋白的表达得以维持，表明其具有向基质分化的潜力。17.94细胞系含有TP53突变，这与原始肿瘤的间变性组织学一致，但缺乏WT1、WTX或β - 连环蛋白1（CTNNB1）的突变，这些是参与WT发病机制的其他基因。17.94细胞在7p、11p或16q处未显示杂合性缺失；然而，在几个位点检测到DNA高甲基化，包括H19差异甲基化区域（表明11p15处胰岛素样生长因子2（IGF2）印记丢失）和5q31处的原钙黏蛋白（PCDH）@基因簇。17.94细胞系的建立应有助于进一步剖析WT发病机制中涉及的遗传 - 表观遗传相互作用。
