SOMATIC INACTIVATION OF GENES ON CHROMOSOME-13 IS A COMMON EVENT IN RETINOBLASTOMA
SOMATIC INACTIVATION OF GENES ON CHROMOSOME-13 IS A COMMON EVENT IN RETINOBLASTOMA
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DOI：
10.1038/304451a0
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发表时间：
1983-01-01
期刊：
影响因子：
64.8
通讯作者：
PHILLIPS, RA
中科院分区：
文献类型：
--
作者：
GODBOUT, R;DRYJA, TP;PHILLIPS, RA
通过对先天性染色体异常患者的家族研究和分析，导致视网膜母细胞瘤这种眼部肿瘤遗传形式的种系突变被确定在13号染色体上的q14区域，并与一种名为酯酶D （ESD）的酶密切相关。Knudson提出，在遗传性视网膜母细胞瘤3患者中，除了生殖系突变外，只需一个体细胞事件就能诱发肿瘤；非遗传形式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13ql4剩余正常基因的突变或基因组中另一位点的基因突变。在这里，我们检查了6例视网膜母细胞瘤患者，他们的电泳变异是杂合的。尽管所有6名患者的正常细胞都表达这两种变体，但4名患者的肿瘤细胞仅表达来自两个ESD等位基因中的一个的酶。我们初步得出结论，视网膜母细胞瘤肿瘤的诱导需要ESD位点附近基因的体细胞失活，包括视网膜母细胞瘤（RB）位点上剩余的正常基因。
Through family studies1and analysis of patients with congenital chromosome abnormalities2, 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 retinoblastoma3; 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 13ql4 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.