Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families.-猫眼课题宝

DOI：

发表时间：

1994-03

期刊：

Cancer research

影响因子：

11.2

通讯作者：

中科院分区：

医学1区

文献类型：

作者：

Julian;M. Birch;A. Hartley;K. Tricker;Jane Presser;Alison;Condie;A. Kelsey;Martin;Harris;Patricia;H. M. Jones;Áine Binchy;D. Crowther;A. Craft;Osborne;B. Eden;D. Gareth;R. Evans;E. B. Thompson;R. Mann;John F Martin;E. Mitchell;Mauro F. SantibÃ

对 p53 基因的整个编码序列进行了分析，以确定 12 个符合 Li-Fraumeni 综合征（经典 LFS）限制性定义的家族和 9 个具有符合更广泛定义的 LFS 特征的家族中是否存在突变。在七个家庭中检测到突变。六个是点突变，其中一个影响密码子 175、180 和 220，三个影响密码子 248。第七个是外显子 4 中的缺失/插入突变。p53 的种系突变是包括患有横纹肌肉瘤和/或肾上腺皮质癌的儿童的家族的一个特征。在患有此类肿瘤的 9 个家庭中，有 6 个家庭检测到种系 p53 突变。对这 7 个突变以及 34 个已发表的实例的分析表明，一半以上是 CpG 二核苷酸的转变，表明大多数种系 p53 突变可能是自发事件的结果。 41个种系p53突变家族中最常见的癌症与经典LFS一样，是骨和软组织肉瘤、乳腺癌、脑肿瘤、白血病和肾上腺皮质癌，尽管只有不到一半的种系p53突变先证者来自经典LFS家族。超过一半的癌症和近三分之一的乳腺癌是在 30 岁之前被诊断出来的。这些观察结果对于种系 p53 突变的无症状携带者具有重要意义，并且需要在制定管理此类家庭的方案方面进行国际合作。

The entire coding sequence of the p53 gene was analysed for the presence of mutations in 12 families conforming to a restricted definition of Li-Fraumeni syndrome (classic LFS) and nine families with features of LFS conforming to a broader definition. Mutations were detected in seven families. Six were point mutations with one each affecting codons 175, 180, and 220 and three affecting codon 248. The seventh was a deletion/insertion mutation in exon 4. Germline mutations in p53 were a feature of families which included children with rhabdomyosarcoma and/or adrenal cortical carcinoma. Germline p53 mutations were detected in six of the nine families with such tumors. An analysis of these 7 mutations, together with 34 published examples, showed that more than one-half were transitions at CpG dinucleotides, suggesting that the majority of germline p53 mutations may arise as a result of spontaneous events. The most common cancers occurring in the 41 families with germline p53 mutations, in common with classic LFS, were bone and soft tissue sarcoma, breast cancer, brain tumors, leukemia, and adrenocortical carcinoma, although less than one-half of the probands with germline p53 mutations came from classic LFS families. More than one-half of the cancers overall and nearly one-third of the breast cancers were diagnosed before 30 years of age. These observations have important implications for asymptomatic carriers of germline p53 mutations, and there is a need for international collaboration in the development of protocols for the management of such families.

Prevalence and diversity of constitutional mutations in the p53 gene among 21 Li-Fraumeni families.

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