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  • Title: Detection of both mutant and wild-type p53 protein in normal skin fibroblasts and demonstration of a shared 'second hit' on p53 in diverse tumors from a cancer-prone family with Li-Fraumeni syndrome.
    Author: Srivastava S, Tong YA, Devadas K, Zou ZQ, Sykes VW, Chen Y, Blattner WA, Pirollo K, Chang EH.
    Journal: Oncogene; 1992 May; 7(5):987-91. PubMed ID: 1373881.
    Abstract:
    Germline transmission of mutant p53 gene in cancer-prone families with Li-Fraumeni syndrome has revealed a new role for p53 in the genetic predisposition to cancer. The studies reported here focus on the analysis of the expression of normal and mutant p53 RNA and protein in germline configuration and demonstrate that normal skin fibroblasts derived from members of a family with Li-Fraumeni syndrome express mutant p53Gly----Asp(245) protein and RNA at levels similar to the wild-type p53. Thus, these fibroblasts represent a unique biological system in which endogenous promoters are utilized for the expression of both mutant and normal p53. We have further extended the earlier observations on the analysis of mutant p53 with a limited number of tumors derived from individuals with Li-Fraumeni syndrome. Tumors arising from two different germ layers in four individuals in a single family clearly exhibited the loss of the wild-type allele and the retention of the mutant allele observed in the normal skin fibroblasts derived from the same individuals. These observations further support the notion that germline p53 mutation plays a key role in the tumorigenesis of individuals with Li-Fraumeni syndrome.
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