Grundy P E, Telzerow P E, Breslow N, Moksness J, Huff V, Paterson M C
Department of Pediatrics, Cross Cancer Institute, Edmonton, Alberta, Canada.
Cancer Res. 1994 May 1;54(9):2331-3.
We have prospectively analyzed Wilms' tumors from 232 patients registered on the National Wilms' Tumor Study for loss of heterozygosity (LOH) on chromosomes 11p, 16q, and 1p. These chromosomal aberrations were found in 70 (33%), 35 (17%), and 21 (12%) of the informative cases, respectively. LOH for two of these regions occurred in only 25 cases, and only one tumor harbored LOH at all three sites. There was no statistically significant association between LOH at any of the three regions and either the stage or histological classification of the tumor. Patients with tumor-specific LOH for chromosome 16q had relapse rates 3.3 times higher (P = 0.01) and mortality rates 12 times higher (P < 0.01) than patients without LOH for chromosome 16q. These differences remained when adjusted for histology or for stage. Patients with LOH for chromosome 1p had relapse and mortality rates three times higher than those for patients without LOH for chromosome 1p, but these results were not statistically significant. In contrast, LOH for chromosome 11p had no effect on measures of outcome. These molecular markers may serve to further stratify Wilms' tumor patients into biologically favorable and unfavorable subgroups, allowing continued use of the clinical trial mechanism in the study of Wilms' tumor.
我们对参加国家肾母细胞瘤研究登记的232例患者的肾母细胞瘤进行了前瞻性分析，以检测11p、16q和1p染色体上的杂合性缺失（LOH）。在信息充分的病例中，这些染色体畸变分别在70例（33%）、35例（17%）和21例（12%）中被发现。仅在25例病例中出现了其中两个区域的LOH，只有1例肿瘤在所有三个位点均存在LOH。这三个区域中任何一个区域的LOH与肿瘤的分期或组织学分类之间均无统计学意义上的显著关联。与16q染色体无LOH的患者相比，16q染色体存在肿瘤特异性LOH的患者复发率高3.3倍（P = 0.01），死亡率高12倍（P < 0.01）。在对组织学或分期进行校正后，这些差异仍然存在。1p染色体存在LOH的患者复发率和死亡率比1p染色体无LOH的患者高3倍，但这些结果无统计学意义。相比之下，11p染色体的LOH对预后指标没有影响。这些分子标志物可能有助于将肾母细胞瘤患者进一步分层为生物学上预后良好和不良的亚组，从而在肾母细胞瘤研究中继续采用临床试验机制。
