A NOVEL GERMLINE P53 SPLICING MUTATION IN A PEDIATRIC-PATIENT WITH A 2ND MALIGNANT NEOPLASM

Citation
Ca. Felix et al., A NOVEL GERMLINE P53 SPLICING MUTATION IN A PEDIATRIC-PATIENT WITH A 2ND MALIGNANT NEOPLASM, Oncogene, 8(5), 1993, pp. 1203-1210
Citations number
44
Journal title
ISSN journal
09509232
Volume
8
Issue
5
Year of publication
1993
Pages
1203 - 1210
Database
ISI
SICI code
0950-9232(1993)8:5<1203:ANGPSM>2.0.ZU;2-2
Abstract
A novel germline p53 splicing mutation was identified in a pediatric p atient with two metachronous primary cancers that are constituent tumo rs of the Li-Fraumeni syndrome. Genomic DNA from the second tumor show ed the same mutation and loss of heterozygosity at the p53 locus. The mutant mRNA and protein were present in the tumor tissue. In contrast, in the normal tissues bearing the germline mutation in the heterozygo us state, predominantly normal mRNA was expressed and the mutant p53 p rotein was not detectable. The functional silence and relative lack of mutant p53 mRNA expression in the normal tissues of this patient may be caused by decreased stability or decreased production. If this prov es a more general pattern of expression of mutant p53 in individuals w ith germline mutations, these findings may explain the paucity of tumo rs in individuals affected with the Li-Fraumeni syndrome.