title: Screening for TP53 rearrangements in families with the Li-Fraumeni syndrome reveals a complete deletion of the TP53 gene.
abstract: 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 LFS, 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.
authors.affiliation: Inserm EMI 9906-IFRMP, Faculty of Medicine, Rouen, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Bougeard
authors.forename: Laurence
authors.initials: L
authors.lastname: Brugières
authors.forename: Agnès
authors.initials: A
authors.lastname: Chompret
authors.forename: Paul
authors.initials: P
authors.lastname: Gesta
authors.forename: Françoise
authors.initials: F
authors.lastname: Charbonnier
authors.forename: Alexander
authors.initials: A
authors.lastname: Valent
authors.forename: Cosette
authors.initials: C
authors.lastname: Martin
authors.forename: Grégory
authors.initials: G
authors.lastname: Raux
authors.forename: Jean
authors.initials: J
authors.lastname: Feunteun
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bressac-de Paillerets
authors.forename: Thierry
authors.initials: T
authors.lastname: Frébourg
mesh_terms: D017931:DNA Primers; D005260:Female; D017353:Gene Deletion; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D008297:Male; D010375:Pedigree; D012509:Sarcoma / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D017931:DNA Primers