Oncogenic point mutations in the human retinoblastoma gene: their application to genetic counseling.
Oncogenic point mutations in the human retinoblastoma gene: their application to genetic counseling.
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DOI：
10.1056/nejm198912213212501
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发表时间：
1989-12
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影响因子：
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通讯作者：
D. Yandell;T. Campbell;Siri H. Dayton;R. Petersen;David Walton;J. Little;Allyn McConkie-Rosell;E. Buckley;T. Dryja
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文献类型：
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作者：
D. Yandell;T. Campbell;Siri H. Dayton;R. Petersen;David Walton;J. Little;Allyn McConkie-Rosell;E. Buckley;T. Dryja
视网膜母细胞瘤基因的突变，其中大部分不能通过常规的Southern印迹检测到，已知会导致视网膜母细胞瘤的非遗传性和遗传性形式，并与其他癌症的发展有关。非遗传性视网膜母细胞瘤由体细胞突变引起。遗传性视网膜母细胞瘤是由生殖细胞突变引起的，通常是一种新的突变，因此通常没有这种疾病的家族史。与非遗传性疾病患者不同，遗传性形式的患者有患其他视网膜母细胞瘤的风险，他们的后代也有患肿瘤的风险。我们使用了一种灵敏的引物定向酶扩增技术，然后进行DNA序列分析，从7例单纯性视网膜母细胞瘤患者（无家族病史）的肿瘤中鉴定出小至单核苷酸变化的突变。在4名患者中，突变仅涉及肿瘤细胞，在3名患者中，它涉及正常体细胞以及肿瘤细胞，但在父母中均未发现;因此，这些突变似乎是新的生殖细胞突变。此外，我们还在一个膀胱癌、一个小细胞肺癌和另一个视网膜母细胞瘤的细胞中发现了点突变。我们的结论是，我们所描述的技术可以区分遗传性和非遗传性视网膜母细胞瘤，它是有用的风险估计和遗传咨询。
Mutations of the retinoblastoma gene, most of which cannot be detected by conventional Southern blotting, are known to cause both the nonhereditary and hereditary forms of retinoblastoma and have been implicated in the development of other cancers. Nonhereditary retinoblastoma is caused by a somatic mutation. Hereditary retinoblastoma is caused by a germ-cell mutation, most often a new one, and thus there is usually no family history of the disease. Unlike patients with the nonhereditary disease, those with the hereditary form are at risk for additional retinoblastomas, and their progeny are at risk for the tumors. We used a sensitive technique of primer-directed enzymatic amplification, followed by DNA sequence analysis, to identify mutations as small as a single nucleotide change in tumors from seven patients with simplex retinoblastoma (with no family history of the disease). In four patients the mutation involved only the tumor cells, and in three it involved normal somatic cells as well as tumor cells but was not found in either parent; thus, these mutations appeared to be new, germ-cell mutations. In addition, we found point mutations in cells from a bladder carcinoma, a small-cell carcinoma of the lung, and another retinoblastoma. We conclude that the technique that we have described can distinguish hereditary from nonhereditary retinoblastoma and that it is useful in risk estimation and genetic counseling.