Leblanc T, Soussi T
Service d'hématologie pédiatrique, hôpital Saint-Louis, Paris, France.
Arch Pediatr. 1994 Jan;1(1):61-70.
The eponym Li-Fraumeni syndrome is given to a particular form of cancer-prone family in which the main encountered tumors are sarcomas occurring in childhood and breast cancers affecting young adult females. There is also an increased frequency of cerebral tumors, leukemias and adrenal carcinomas among these families. The transmission of the cancer-proneness is autosomal dominant and related to the loss of function of the p53 tumor suppressor gene located on the short arm of the chromosome 17. The related p53 protein is identified but its precise mechanism of action and its regulation are still unclear. It seems to activate the genes which negatively regulate the multiplication of the cell and to act as a factor of transcription. A germline mutation of the p53 gene must be looked for in every cancer-prone family but also in case of multifocal tumors, particularly osteosarcomas and glioblastomas, and in case of second malignant neoplasm. This is of major scientific as well clinical interest. Indeed, the study of new families will help to better understand the molecular mechanisms underlying the syndrome. For the family itself this allow to identify the cancer prone members and to offer them preventive measures and early detection of cancers, particularly early breast cancer detection.
以李-弗劳梅尼综合征命名的是一种特殊的癌症高发家族类型，其中主要出现的肿瘤是儿童期发生的肉瘤以及影响年轻成年女性的乳腺癌。在这些家族中，脑肿瘤、白血病和肾上腺癌的发病率也有所增加。癌症易感性的遗传方式为常染色体显性遗传，与位于17号染色体短臂上的p53肿瘤抑制基因功能丧失有关。相关的p53蛋白已被识别，但其确切的作用机制及其调控仍不清楚。它似乎能激活对细胞增殖起负调控作用的基因，并作为一种转录因子发挥作用。在每个癌症高发家族中，以及在多灶性肿瘤（特别是骨肉瘤和胶质母细胞瘤）的情况下，以及在发生第二原发性恶性肿瘤的情况下，都必须寻找p53基因的种系突变。这具有重大的科学和临床意义。事实上，对新家族的研究将有助于更好地理解该综合征背后的分子机制。对于家族本身而言，这有助于识别癌症易感成员，并为他们提供预防措施和癌症早期检测，特别是早期乳腺癌检测。
