Felix C A, Strauss E A, D'Amico D, Tsokos M, Winter S, Mitsudomi T, Nau M M, Brown D L, Leahey A M, Horowitz M E
Department of Pediatrics, Children's Hospital of Philadelphia, Pennsylvania 19104.
Oncogene. 1993 May;8(5):1203-10.
A novel germline p53 splicing mutation was identified in a pediatric patient with two metachronous primary cancers that are constituent tumors of the Li-Fraumeni syndrome. Genomic DNA from the second tumor showed the same mutation and loss of heterozygosity at the p53 locus. The mutant mRNA and protein were present in the tumor tissue. In contrast, in the normal tissues bearing the germline mutation in the heterozygous state, predominantly normal mRNA was expressed and the mutant p53 protein was not detectable. The functional silence and relative lack of mutant p53 mRNA expression in the normal tissues of this patient may be caused by decreased stability or decreased production. If this proves a more general pattern of expression of mutant p53 in individuals with germline mutations, these findings may explain the paucity of tumors in individuals affected with the Li-Fraumeni syndrome.
在一名患有两种异时性原发性癌症（这两种癌症是李-弗劳梅尼综合征的组成性肿瘤）的儿科患者中，鉴定出一种新的种系p53剪接突变。来自第二个肿瘤的基因组DNA显示在p53基因座处存在相同的突变和杂合性缺失。肿瘤组织中存在突变的mRNA和蛋白质。相比之下，在以杂合状态携带种系突变的正常组织中，主要表达正常的mRNA，且未检测到突变的p53蛋白。该患者正常组织中突变p53 mRNA表达的功能沉默和相对缺乏可能是由于稳定性降低或产生减少所致。如果这被证明是种系突变个体中突变p53表达的更普遍模式，这些发现可能解释了李-弗劳梅尼综合征患者中肿瘤数量较少的原因。
