GERM-LINE EXCLUSION OF A SINGLE P53 ALLELE BY PREMATURE TERMINATION OF TRANSLATION IN A LI-FRAUMENI SYNDROME FAMILY

被引:0
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作者
STOLZENBERG, MC
BRUGIERES, L
GARDES, M
DESSARPSFREICHEY, F
CHOMPRET, A
BRESSAC, B
LENOIR, G
BONAITIPELLIE, C
LEMERLE, J
FEUNTEUN, J
机构
[1] INST GUSTAVE ROUSSY,ONCOL MOLEC LAB,CNRS,URA 1158,F-94805 VILLEJUIF,FRANCE
[2] INST GUSTAVE ROUSSY,DEPT PEDIAT ONCOL,F-94805 VILLEJUIF,FRANCE
[3] INSERM,U155,UNITE RECH EPIDEMIOL GENET,F-75016 PARIS,FRANCE
[4] INST GUSTAVE ROUSSY,UNITE DIAGNOST MOLEC,F-94805 VILLEJUIF,FRANCE
[5] INT AGCY RES CANC,F-69372 LYON 08,FRANCE
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中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Germline p53 mutations have been detected in approximately half of the families affected by the Li-Fraumeni syndrome (LFS), in which they are believed to represent the genetic status predisposing to multiple cancers. Failure to detect mutations in the other half of LFS families suggests that sequence analysis, which has been limited to the p53 gene coding region, have overlooked other genetic events lying outside of this region or/and that alterations in other gene(s) than p53 may also lead to the syndrome. In this report, we present the evidence that a single base pair deletion in the p53 coding sequence, leading to premature signal termination of translation, generates a null allele by preventing transport of mutant allele mRNAs into the cytoplasm. This allelic exclusion which confers a status of unizygote vis-a-vis the wild-type p53 gene to individuals who carry the mutant allele, leads to predisposition to multiple cancers in a Li-Fraumeni family. Thus, the loss of the wild-type p53 allele appears as the rate limiting step in tumor induction.
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页码:2799 / 2804
页数:6
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