Gessler M, König A, Arden K, Grundy P, Orkin S, Sallan S, Peters C, Ruyle S, Mandell J, Li F
Institut für Humangenetik, Philipps-Universität, Marburg, Germany.
Hum Mutat. 1994;3(3):212-22. doi: 10.1002/humu.1380030307.
Homozygous deletions in Wilms' tumor DNA have been a key step in the identification and isolation of the WT1 gene. Several additional loci are also postulated to contribute to Wilms' tumor formation. To assess the frequency of WT1 alterations we have analyzed the WT1 locus in a panel of 77 Wilms' tumors. Eight tumors showed evidence for large deletions of several hundred or thousand kilobasepairs of DNA, some of which were also cytogenetically detected. Additional intragenic mutations were detected using more sensitive SSCP analyses to scan all 10 WT1 exons. Most of these result in premature stop codons or missense mutations that inactivate the remaining WT1 allele. The overall frequency of WT1 alterations detected with these methods is less than 15%. While some mutations may not be detectable with the methods employed, our results suggest that direct alterations of the WT1 gene are present in only a small fraction of Wilms' tumors. Thus, mutations at other Wilms' tumor loci or disturbance of interactions between these genes likely play an important role in Wilms' tumor development.
肾母细胞瘤DNA中的纯合缺失是鉴定和分离WT1基因的关键步骤。还推测有几个其他基因座与肾母细胞瘤的形成有关。为了评估WT1改变的频率，我们分析了一组77例肾母细胞瘤中的WT1基因座。8个肿瘤显示有几百或几千千碱基对DNA的大片段缺失证据，其中一些也通过细胞遗传学检测到。使用更敏感的单链构象多态性（SSCP）分析来扫描WT1基因的所有10个外显子，检测到了其他基因内突变。其中大多数导致过早的终止密码子或错义突变，从而使剩余的WT1等位基因失活。用这些方法检测到的WT1改变的总体频率小于15%。虽然使用的方法可能检测不到一些突变，但我们的结果表明，WT1基因的直接改变仅存在于一小部分肾母细胞瘤中。因此，其他肾母细胞瘤基因座的突变或这些基因之间相互作用的紊乱可能在肾母细胞瘤的发展中起重要作用。
