Hoban P R, Heighway J, White G R, Baker B, Gardner J, Birch J M, Morris-Jones P, Kelsey A M
CRC Department of Cancer Genetics, Paterson Institute of Cancer Research, Christie (CRC) Research Trust, Manchester, UK.
Hum Genet. 1995 Jun;95(6):651-6. doi: 10.1007/BF00209482.
A patient with Beckwith-Wiedemann syndrome (BWS) presented with Wilms' tumour. Examination of the nephrectomy specimen showed, in addition to the tumour, the presence of nephrogenic rests. Nephrogenic rests are thought to be precursor lesions from which a Wilms' tumour may develop. A molecular analysis examining the loss of constitutional heterozygosity (LOCH), initially for chromosome 11, was performed on peripheral blood, the normal kidney, nephrogenic rest and tumour material. The study was extended to include markers from all 23 chromosomes. At each informative, locus, LOCH of the maternal allele was shown in the nephrogenic rest and tumour material. In addition, the normal kidney displayed allele imbalance. It would appear from these results that either extensive LOCH across the genome was an early genetic event in the development of malignancy in this patient or that the tumour and rest developed from cells containing no maternal chromosomes. The apparent LOCH seen in the normal kidney sample implies that full reduction to homozygosity is consistent with a histologically normal appearance. Putative mechanisms to explain this phenomenon are discussed.
一名患有贝克威思-维德曼综合征（BWS）的患者出现了肾母细胞瘤。对肾切除标本的检查显示，除肿瘤外，还存在肾源性残留。肾源性残留被认为是肾母细胞瘤可能从中发展而来的前体病变。对患者的外周血、正常肾脏、肾源性残留和肿瘤组织进行了分子分析，最初检测11号染色体的体细胞杂合性缺失（LOCH），之后该研究扩展到包括所有23条染色体的标记物。在每个信息位点，肾源性残留和肿瘤组织中均显示母本等位基因的LOCH。此外，正常肾脏表现出等位基因失衡。从这些结果来看，要么全基因组广泛的LOCH是该患者恶性肿瘤发生过程中的早期遗传事件，要么肿瘤和残留是由不含母本染色体的细胞发展而来。在正常肾脏样本中观察到的明显LOCH表明完全纯合化与组织学上的正常外观是一致的。文中讨论了解释这一现象的可能机制。
