MacGeoch C, Turner G, Bobrow L G, Barnes D M, Bishop D T, Spurr N K
Imperial Cancer Research Fund Human Genetic Resources, Clare Hall Laboratories, South Mimms, Potters Bar, UK.
J Med Genet. 1995 Mar;32(3):186-90. doi: 10.1136/jmg.32.3.186.
We have screened two families for constitutional TP53 mutations, one family with Li-Fraumeni syndrome and the other with features of this syndrome. We report a germline mutation in exon 7 of the TP53 gene in the family with "Li-Fraumeni-like" syndrome. The mutation occurred at codon 245 and causes a Gly-Ser amino acid change. It was inherited by both affected and unaffected subjects. Malignant tumours from all members of this family showed strong positive nuclear immunohistochemical staining with antibodies CM-1 and DO1, directed against TP53. In contrast, no constitutional TP53 mutations were found in a "classic" Li-Fraumeni family. In this family positive staining was seen in both malignant and normal tissues. These results support previous findings that variants of the Li-Fraumeni syndrome exist since not all LFS families carry TP53 germline mutations. Secondly, immunohistochemical positivity is not synonymous with an underlying mutation and is therefore inadequate as an exclusive diagnostic marker.
我们对两个家族进行了遗传性TP53突变筛查，一个家族患有李-弗劳梅尼综合征，另一个家族有该综合征的特征。我们报告了一个“类李-弗劳梅尼”综合征家族中TP53基因第7外显子的种系突变。该突变发生在第245密码子，导致甘氨酸-丝氨酸氨基酸改变。它由患病和未患病的个体遗传。这个家族所有成员的恶性肿瘤用针对TP53的抗体CM-1和DO1进行核免疫组织化学染色均呈强阳性。相比之下，在一个“典型”的李-弗劳梅尼家族中未发现遗传性TP53突变。在这个家族中，恶性组织和正常组织均可见阳性染色。这些结果支持了先前的发现，即李-弗劳梅尼综合征存在变异型，因为并非所有李-弗劳梅尼综合征家族都携带TP53种系突变。其次，免疫组织化学阳性并不等同于存在潜在突变，因此作为唯一的诊断标志物是不充分的。
