Mason J E, Goodfellow P J, Grundy P E, Skinner M A
Department of Surgery, Washington University School of Medicine, St Louis, Missouri, USA.
J Pediatr Surg. 2000 Jun;35(6):891-6; discussion 896-7. doi: 10.1053/jpsu.2000.6911.
BACKGROUND/PURPOSE: Wilms' tumor is the most common renal malignancy of childhood. Loss of heterozygosity (LOH) at 16q is seen in about 17% of cases and has been associated with a poor prognosis. To more precisely define the pattern of 16q deletion exhibited by Wilms' tumor, the authors performed a detailed LOH analysis of 96 specimens using polymorphic microsatellite repeat markers. The authors also evaluated the neoplasms for the presence of microsatellite instability (MSI).
A total of 96 DNA samples were studied using polymerase chain reaction-based LOH analyses amplifying polymorphic microsatellite repeat markers. Screening for MSI using 2 additional genetic markers also was carried out.
The authors found 16q LOH in 14 of the specimens evaluated. Comprehensive analysis of these LOH-positive specimens showed a region of loss spanning 16p11.2-q22.1 and a separate distal region of LOH at 16q23.2-24.2. The distal region of deletion is very small, estimated to be approximately 2.4 megabases. In addition to the observed LOH, 2 specimens were found to consistently exhibit MSI, which has not been reported previously in Wilms' tumor.
The smallest consensus region of deletion in our analysis of Wilms' tumor 16q LOH measures 2.4 megabases at 16q23.2-q24.2. Additionally, MSI was present in a subset of tumor specimens suggesting that defects in DNA mismatch repair may contribute to the pathogenesis of Wilms' tumor.
背景/目的：肾母细胞瘤是儿童期最常见的肾脏恶性肿瘤。16号染色体长臂（16q）杂合性缺失（LOH）在约17%的病例中可见，且与预后不良相关。为更精确地界定肾母细胞瘤所表现出的16q缺失模式，作者使用多态性微卫星重复标记对96份标本进行了详细的LOH分析。作者还评估了肿瘤中微卫星不稳定性（MSI）的存在情况。
使用基于聚合酶链反应的LOH分析，扩增多态性微卫星重复标记，对总共96份DNA样本进行研究。还使用另外2个遗传标记进行MSI筛查。
作者在评估的14份标本中发现了16q LOH。对这些LOH阳性标本的综合分析显示，缺失区域跨越16p11.2 - q22.1，以及16q23.2 - 24.2处一个单独的远端LOH区域。远端缺失区域非常小，估计约为2.4兆碱基对。除了观察到的LOH外，还发现2份标本始终表现出MSI，这在肾母细胞瘤中此前尚未有报道。
在我们对肾母细胞瘤16q LOH的分析中，最小的共同缺失区域在16q23.2 - q24.2处，大小为2.4兆碱基对。此外，一部分肿瘤标本中存在MSI，提示DNA错配修复缺陷可能在肾母细胞瘤的发病机制中起作用。
