Screening for TP53 rearrangements in families with the Li-Fraumeni syndrome reveals a complete deletion of the TP53 gene

被引:49
作者
Bougeard, G
Brugières, L
Chompret, A
Gesta, P
Charbonnier, F
Valent, A
Martin, C
Raux, G
Feunteun, J
Bressac-de Paillerets, B
Frébourg, T [1 ]
机构
[1] IFRMP, Fac Med, INSERM, EMI 9906, F-76183 Rouen, France
[2] Inst Gustave Roussy, Dept Pediat, F-94805 Villejuif, France
[3] Ctr Hosp, F-79021 Niort, France
[4] CHU Rouen, Dept Genet, Rouen, France
[5] Inst Gustave Roussy, Dept Cellular Genom Canc, F-94805 Villejuif, France
[6] Inst Gustave Roussy, UMR 8125, F-94805 Villejuif, France
[7] Inst Gustave Roussy, Dept Biol Clin, F-94805 Villejuif, France
关键词
TP53; Li-Fraumeni syndrome; deletion; PCR;
D O I
10.1038/sj.onc.1206155
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
The absence of detectable germline TP53 mutations in a fraction of families with Li-Fraumeni syndrome (LFS) has suggested the involvement of other genes, but this hypothesis remains controversial. The density of Alu repeats within the TP53 gene led us to search genomic rearrangements of TP53 in families without detectable TP53 mutation. To this aim, we adapted the quantitative multiplex PCR of short fluorescent fragments (QMPSF) method to the analysis of the 11 exons of TP53. We analysed 98 families, either fulfilling (six families) or partially meeting (92 families) the criteria for LFS, and in which classical methods had failed to reveal TP53 alterations. We identified, in a large family fulfilling the criteria for LITS, a complete heterozygous deletion of TP53. Additional QMPSF analyses indicated that this deletion, which partially removed the centromeric FLJ10385 locus, covered approximately 45 kb. This deletion was shown to result from a complex rearrangement involving two distinct Alu-mediated recombinations. We conclude that TP53 germline rearrangements occur as rare events, but must be considered in LFS families without detectable point TP53 mutation.
引用
收藏
页码:840 / 846
页数:7
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