PREFERENTIAL GERMLINE MUTATION OF THE PATERNAL ALLELE IN RETINOBLASTOMA
PREFERENTIAL GERMLINE MUTATION OF THE PATERNAL ALLELE IN RETINOBLASTOMA
复制标题
DOI：
10.1038/340312a0
复制
发表时间：
1989-07-27
期刊：
影响因子：
64.8
通讯作者：
GALLIE, BL
中科院分区：
文献类型：
--
作者：
ZHU, XP;DUNN, JM;GALLIE, BL
在70%的视网膜母细胞瘤肿瘤中触发恶性增殖的事件是染色体13 ql 4的杂合性丢失，由此正常的视网膜母细胞瘤基因（RB 1）等位基因丢失，并且已经突变的RB 1等位基因保留在肿瘤中1 -3。第一个等位基因遭受突变事件-缺失，重复或点突变（手稿在准备中）-在生殖细胞（所有双侧患者）或体视网膜细胞（大多数单侧患者）中。大多数双侧患者没有视网膜母细胞瘤的家族史，并被推测有新的生殖细胞突变，这些突变发生在卵子、精子或早期胚胎中。我们已经确定了父母的起源保留的等位基因在9视网膜母细胞瘤肿瘤从8个无关的非家族性的情况下，通过使用RB 1连锁遗传标记。六个肿瘤保留了父亲的等位基因，三个保留了母亲的等位基因。在三个单侧肿瘤中，只有一个保留了父亲的RB 1等位基因。因此，没有证据表明，父亲的RB 1等位基因优先保留在视网膜母细胞瘤，已被认为是在骨肉瘤的情况下4，5。相比之下，5名双侧患者中有4名的肿瘤保留了父亲的RB 1等位基因。这表明，在精子发生过程中比在卵子发生过程中更频繁地出现新的生殖系RB 1突变，或者早期胚胎中的印记影响染色体对突变的易感性。
THE event triggering malignant proliferation in 70% of retinoblastoma tumours is loss of heterozygosity for chromosome 13ql4, whereby the normal retinoblastoma gene (RB1) allele is lost and an already mutated RB1 allele remains in the tumour1-3. The first allele suffers a mutational event—deletion, duplication or point mutation (manuscript in preparation)—either in the germ line (all bilateral patients) or in a somatic retinal cell (most unilateral patients). Most bilateral patients have no family history of retinoblastoma and are presumed to have new germline mutations which arose in the egg, sperm or early embryo. We have determined the parental origin of the retained allele in nine retinoblastoma tumours from eight unrelated non-familial cases by using RB1-linked genetic markers. Six tumours retained the paternal allele and three retained the maternal allele. Of the three unilateral tumours, only one retained the paternal RB1 allele. Thus, there is no evidence that the paternal RB1 allele is preferentially retained in retinoblastoma, as has been suggested to be the case in osteosar-coma4,5. By contrast, tumours from four of the five bilateral patients retained the paternal RB1 allele. This suggests either that new germline RB1 mutations arise more frequently during sper-matogenesis than during oogenesis, or that imprinting in the early embryo affects chromosomal susceptibility to mutation.