家族性腺瘤性息肉病中隐匿性突变的分析
Analysis of masked mutations in familial adenomatous polyposis.
作者信息
Laken S J, Papadopoulos N, Petersen G M, Gruber S B, Hamilton S R, Giardiello F M, Brensinger J D, Vogelstein B, Kinzler K W
机构信息
The Johns Hopkins Oncology Center, 424 North Bond Street, Baltimore, MD 21231, USA.
出版信息
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2322-6. doi: 10.1073/pnas.96.5.2322.
Familial adenomatous polyposis (FAP) is an autosomal-dominant disease characterized by the development of hundreds of adenomatous polyps of the colorectum. Approximately 80% of FAP patients can be shown to have truncating mutations of the APC gene. To determine the cause of FAP in the other 20% of patients, MAMA (monoallelic mutation analysis) was used to independently examine the status of each of the two APC alleles. Seven of nine patients analyzed were found to have significantly reduced expression from one of their two alleles whereas two patients were found to have full-length expression from both alleles. We conclude that more than 95% of patients with FAP have inactivating mutations in APC and that a combination of MAMA and standard genetic tests will identify APC abnormalities in the vast majority of such patients. That no APC expression from the mutant allele is found in some FAP patients argues strongly against the requirement for dominant negative effects of APC mutations. The results also suggest that there may be at least one additional gene, besides APC, that can give rise to FAP.
家族性腺瘤性息肉病（FAP）是一种常染色体显性疾病，其特征是在结肠直肠出现数百个腺瘤性息肉。大约80%的FAP患者可检测到APC基因的截短突变。为了确定另外20%患者患FAP的病因，采用单等位基因突变分析（MAMA）独立检测两个APC等位基因各自的状态。在分析的9名患者中，有7名患者的两个等位基因之一的表达显著降低，而另外两名患者的两个等位基因均有全长表达。我们得出结论，超过95%的FAP患者在APC基因存在失活突变，并且MAMA与标准基因检测相结合将在绝大多数此类患者中识别出APC异常。在一些FAP患者中未发现突变等位基因有APC表达，这有力地反驳了APC突变需要显性负效应的观点。结果还表明，除了APC基因外，可能至少还有一个其他基因可导致FAP。
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