Weir-Thompson E, Condie A, Leonard R C, Prosser J
MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.
Oncogene. 1991 Dec;6(12):2353-6.
Using the hydroxylamine-osmium tetroxide (HOT) technique, we have identified a constitutional point mutation in the retinoblastoma susceptibility gene (RB1) which segregates with the expression of retinoblastoma in five affected family members. One member developed a second primary tumor, a small-cell lung carcinoma (SCLC), which metastasized to the liver. Analysis of liver tumour DNA revealed homozygosity for the constitutional mutation, a G----A transition at the fifth base of intron 21, resulting in the excision of exon 21 from the mRNA. This is the first demonstration of homozygotization of a constitutional RB mutation in a metastatic second primary tumour and underlines the usefulness of the HOT technique for identification of mutations of the RB1 gene.
运用羟胺-四氧化锇（HOT）技术，我们在视网膜母细胞瘤易感基因（RB1）中鉴定出一个遗传性点突变，该突变在五个患病家庭成员中与视网膜母细胞瘤的表现相关联。其中一名成员发生了第二原发性肿瘤，即小细胞肺癌（SCLC），该肿瘤转移至肝脏。对肝肿瘤DNA的分析显示，该遗传性突变呈纯合状态，即内含子21的第五个碱基处发生了G→A转换，导致外显子21从mRNA中缺失。这是转移性第二原发性肿瘤中遗传性RB突变纯合化的首次证明，并强调了HOT技术在鉴定RB1基因突变方面的实用性。
