Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

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

Screening for TP53 rearrangements in families with the Li–Fraumeni syndrome reveals a complete... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Oncogene Springer Journals

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

Loading next page...
 
/lp/springer-journals/screening-for-tp53-rearrangements-in-families-with-the-li-fraumeni-O0Ao6G7kak

References (14)

Publisher
Springer Journals
Copyright
Copyright © 2003 by Nature Publishing Group
Subject
Medicine & Public Health; Medicine/Public Health, general; Internal Medicine; Cell Biology; Human Genetics; Oncology; Apoptosis
ISSN
0950-9232
eISSN
1476-5594
DOI
10.1038/sj.onc.1206155
Publisher site
See Article on Publisher Site

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.

Journal

OncogeneSpringer Journals

Published: Feb 13, 2003

There are no references for this article.