GERM LINE P53 MUTATIONS IN A FAMILIAL SYNDROME OF BREAST-CANCER, SARCOMAS, AND OTHER NEOPLASMS
GERM LINE P53 MUTATIONS IN A FAMILIAL SYNDROME OF BREAST-CANCER, SARCOMAS, AND OTHER NEOPLASMS
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DOI：
10.1126/science.1978757
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发表时间：
1990-11-30
期刊：
影响因子：
56.9
通讯作者：
FRIEND, SH
中科院分区：
文献类型：
--
作者：
MALKIN, D;LI, FP;FRIEND, SH
家族性癌症综合征有助于确定肿瘤抑制基因在癌症发展中的作用。显性遗传的Li-Fraumeni综合征（LFS）是特别感兴趣的，因为在受影响的个体中发生的儿童和成人肿瘤的多样性。LPS的罕见性和高死亡率排除了正式的连锁分析。另一种方法是选择最合理的候选基因。研究肿瘤抑制基因p53是因为先前的迹象表明，该基因在与LFS相关的大多数癌症的散发性（非家族性）形式中失活。在所有分析的5个LFS家族中均检测到生殖系p53突变。这些突变不产生预期对野生型p53蛋白产生反式显性功能丧失效应的突变p53蛋白的量。生殖系p53突变的频率现在可以在其他LFS家族中进行检查，以及其他癌症患者和具有可能归因于突变的临床特征的家族。
Familial cancer syndromes have helped to define the role of tumor suppressor genes in the development of cancer. The dominantly inherited Li-Fraumeni syndrome (LFS) is of particular interest because of the diversity of childhood and adult tumors that occur in affected individuals. The rarity and high mortality of LPS precluded formal linkage analysis. The alternative approach was to select the most plausible candidate gene. The tumor suppressor gene, p53, was studied because of previous indications that this gene is inactivated in the sporadic (nonfamilial) forms of most cancers that are associated with LFS. Germ line p53 mutations have been detected in all five LFS families analyzed. These mutations do not produce amounts of mutant p53 protein expected to exert a trans-dominant loss of function effect on wild-type p53 protein. The frequency of germ line p53 mutations can now be examined in additional families with LFS, and in other cancer patients and families with clinical features that might be attributed to the mutation.