Grundy P, Telzerow P, Moksness J, Breslow N E
Department of Pediatrics, University of Alberta, Edmonton, Canada.
Med Pediatr Oncol. 1996 Nov;27(5):429-33. doi: 10.1002/(SICI)1096-911X(199611)27:5<429::AID-MPO7>3.0.CO;2-O.
Wilms' tumor-specific loss of heterozygosity (LOH) for DNA markers located at chromosomes 11p13, 11p15, 16q, and 1p has been reported to occur in a minority of Wilms' tumors. We hypothesized that tumors classified by region of LOH would exhibit specific clinicopathologic patterns. We have therefore determined the constitutional and tumor genotypes for markers at 11p13, 11p15, 16q, and 1p in a large series of Wilms' tumor patients who were registered on a Pediatric Oncology Group study and on the National Wilms' Tumor Study, to determine whether tumor-specific LOH for any of these regions was associated with any specific phenotype. Of 286 cases, 27% had LOH at both 11p13 and p15 (BOTH), 3% at 11p13 only, 8% at 11p15 only, and 62% at neither. Significant associations were found between younger age at diagnosis and LOH for BOTH, but not for 11p15 only, and between the presence of intralobar nephrogenic rests and LOH for BOTH. The incidence of nephrogenic rests (all types combined) and of bilateral tumors was the same in tumors with or without LOH. There was a negative association between anaplastic histology and LOH for 11p. There was no association between LOH on 11p and outcome as assessed by relapse-free and overall survival. The associations between age at diagnosis and LOH are interpreted as suggesting the existence of a Wilms' tumor locus on 11p in addition to WT1 at 11p13 and the putative WT2 at 11p15. LOH for chromosome 16q was identified in 17% of 204 tumors and was associated with a significantly worse outcome. Outcome for patients with LOH for 1p was also worse but not significantly so.
据报道，位于染色体11p13、11p15、16q和1p的DNA标记在少数肾母细胞瘤中会出现肾母细胞瘤特异性杂合性缺失（LOH）。我们推测，根据LOH区域分类的肿瘤会表现出特定的临床病理模式。因此，我们确定了一大系列在儿童肿瘤学组研究和国家肾母细胞瘤研究中登记的肾母细胞瘤患者在11p13、11p15、16q和1p处标记的体质和肿瘤基因型，以确定这些区域中任何一个区域的肿瘤特异性LOH是否与任何特定表型相关。在286例病例中，27%在11p13和p15均有LOH（两者均有），3%仅在11p13有，8%仅在11p15有，62%两者均无。在诊断时年龄较小与两者均有LOH之间发现了显著关联，但仅与11p15有LOH无关联，并且叶内肾源性残留的存在与两者均有LOH之间也存在关联。有或无LOH的肿瘤中肾源性残留（所有类型合并）和双侧肿瘤的发生率相同。间变组织学与11p的LOH之间存在负相关。根据无复发生存率和总生存率评估，11p的LOH与预后无关联。诊断时年龄与LOH之间的关联被解释为表明除了11p13处的WT1和11p15处的假定WT2之外，11p上还存在一个肾母细胞瘤基因座。在204例肿瘤中有17%鉴定出16号染色体q臂的LOH，并且与显著更差的预后相关。1p有LOH的患者的预后也较差，但差异不显著。
