PREDICTION OF FAMILIAL PREDISPOSITION TO RETINOBLASTOMA
PREDICTION OF FAMILIAL PREDISPOSITION TO RETINOBLASTOMA
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DOI：
10.1056/nejm198605083141901
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发表时间：
1986-05-08
影响因子：
158.5
通讯作者：
NORDENSKJOLD, M
中科院分区：
文献类型：
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作者：
CAVENEE, WK;MURPHREE, AL;NORDENSKJOLD, M
视网膜母细胞瘤是一种儿童癌症，其易感性遗传为常染色体显性性状。我们利用5个视网膜母细胞瘤易感家族的13号染色体上的限制性片段长度和同工酶等位基因，为可能患有肿瘤的人提供疾病前的鉴定。两例预测了患病的可能性，三例预测了免于患病的可能性。在视网膜母细胞瘤（RB1）基因座两侧有信息基因座的病例中，计算出的预测准确性大于94%，我们的预测在每个这样的例子中都得到了满足。一个在几个位点上都有信息的病例表明发生了减数分裂重组，准确的预测是基于DNA标记和酯酶d的同工酶形式获得的数据。在另一个病例中，仅对视网膜母细胞瘤位点远端的位点有信息，计算出的预测精度约为70%。这名患者预计会患上这种疾病，但在一岁时并没有这样做，这说明需要更多的标志物，这些标志物也更有信息量，在基因上更接近视网膜母细胞瘤位点。这些研究为利用任意重组DNA标记进行产前和产后遗传癌症易感性预测提供了基础。这样的预测将使家族性视网膜母细胞瘤的遗传咨询更加准确，并导致更早的肿瘤检测和更有效的治疗。
Retinoblastoma is a childhood cancer, predisposition to which is inherited as an autosomal dominant trait. We used restriction-fragment-length and isozymic alleles of loci on chromosome 13 in five families predisposed to retinoblastoma, to provide identification before illness of persons likely to have tumors. The likelihood of disease was predicted in two cases, and freedom from disease in three. The calculated predictive accuracy was greater than 94 percent in cases with informative loci flanking the retinoblastoma (RB1) locus, and our prediction has been fulfilled in each such instance. A case that was informative at several loci indicated the occurrence of meiotic recombination, and accurate prediction was based on data obtained with DNA markers and isozymic forms of esterase D. The calculated predictive accuracy in another case, which was informative only for loci distal to the retinoblastoma locus, was about 70 percent. This patient was expected to acquire the disease but had not done so at the age of one year, illustrating the need for more markers that are also more informative and genetically closer to the retinoblastoma locus. These studies provide the basis for prenatal and postnatal prediction of susceptibility to inherited cancer using arbitary recombinant DNA markers. Such predictions should make genetic counseling for familial retinoblastoma more accurate and lead to earlier tumor detection and more effective therapy.