Visser M, Sijmons C, Bras J, Arceci R J, Godfried M, Valentijn L J, Voûte P A, Baas F
Department of Pediatric Oncology, Academic Medical Center, Amsterdam, The Netherlands.
Oncogene. 1997 Sep;15(11):1309-14. doi: 10.1038/sj.onc.1201302.
An allelotype covering all autosomes was constructed for the embryonal form of childhood rhabdomyosarcoma (ERMS) in order to identify regions encompassing tumorsuppressor genes (TSG) involved in ERMS. Thusfar most studies were focussed on chromosome 11p15.5, which frequently shows loss of heterozygozity (LOH) in embryonal tumors like RMS and Wilms' tumor (WT). In this study we show that, besides LOH of chromosome 11p15.5 (72%), LOH of chromosome 16q was present in 54% of the tumors analysed. Delineation of these two regions shows that the smallest region of overlap (SRO) for chromosome 11 was between D11S988 and D11S922. This region, estimated to be 7 cM and 3-5 Mb, is also the location of the putative Wilms' tumor WT2 TSG. It contains several genes including IGF2 and potential tumorsuppressor genes like H19 and p57kip2, which might contribute to the carcinogenesis of RMS. Analysis of chromosome 16q LOH defined the SRO between D16S752 and D16S413. LOH of chromosome 16 is also found in other tumors, including WT. Our data suggest that genes involved in the development of RMS and WT may not only be similar for chromosome 11 but also for chromosome 16.
为了确定与儿童横纹肌肉瘤胚胎型(ERMS)相关的肿瘤抑制基因(TSG)所在区域,构建了一个覆盖所有常染色体的等位基因型。到目前为止,大多数研究都集中在染色体11p15.5上,该区域在胚胎性肿瘤如横纹肌肉瘤(RMS)和肾母细胞瘤(WT)中经常显示杂合性缺失(LOH)。在本研究中,我们发现,除了染色体11p15.5的LOH(72%)外,在54%的分析肿瘤中还存在染色体16q的LOH。对这两个区域的划定表明,染色体11的最小重叠区域(SRO)位于D11S988和D11S922之间。该区域估计为7厘摩和3 - 5兆碱基,也是推定的肾母细胞瘤WT2 TSG的位置。它包含几个基因,包括IGF2以及潜在的肿瘤抑制基因如H19和p57kip2,这些基因可能与RMS的致癌作用有关。对染色体16q LOH的分析确定了D16S752和D16S413之间的SRO。在包括WT在内的其他肿瘤中也发现了染色体16的LOH。我们的数据表明,参与RMS和WT发生发展的基因可能不仅在染色体11上相似,在染色体16上也相似。