Godbout R, Dryja T P, Squire J, Gallie B L, Phillips R A
Nature. 1983;304(5925):451-3. doi: 10.1038/304451a0.
Through family studies and analysis of patients with congenital chromosome abnormalities, the germ-line mutation responsible for the hereditary form of the eye tumour, retinoblastoma, has been assigned to the q14 region on chromosome 13 and closely linked to an enzyme called esterase D (ESD). Knudson has proposed that as few as one somatic event in addition to the germ-line mutation is required to induce tumours in patients with the hereditary form of retinoblastoma; the non-hereditary form requires two somatic events to occur in the same cell. The somatic event(s) may involve either mutation of the remaining normal gene at 13q14 or mutation of a gene at another site in the genome. Here we have examined six retinoblastoma patients who are heterozygous for electrophoretic variants of ESD. Although the normal cells of all six patients expressed both variants, the tumour cells of four patients expressed enzyme from only one of the two ESD alleles. We tentatively conclude that induction of a retinoblastoma tumour requires the somatic inactivation of genes near the ESD locus including the remaining normal gene at the retinoblastoma (RB) locus.
通过家族研究以及对先天性染色体异常患者的分析，已将导致遗传性眼肿瘤视网膜母细胞瘤的种系突变定位到13号染色体的q14区域，并与一种名为酯酶D（ESD）的酶紧密连锁。克努森提出，对于遗传性视网膜母细胞瘤患者，除种系突变外，只需少至一个体细胞事件即可诱发肿瘤；非遗传性形式则需要在同一细胞中发生两个体细胞事件。体细胞事件可能涉及13q14处剩余正常基因的突变，或基因组中另一位点基因的突变。在此，我们研究了6名ESD电泳变体杂合的视网膜母细胞瘤患者。尽管所有6名患者的正常细胞均表达两种变体，但4名患者的肿瘤细胞仅表达两个ESD等位基因中一个的酶。我们初步得出结论，视网膜母细胞瘤的诱发需要ESD基因座附近基因的体细胞失活，包括视网膜母细胞瘤（RB）基因座处的剩余正常基因。
