title: A novel germline p53 splicing mutation in a pediatric patient with a second malignant neoplasm.
abstract: A novel germline p53 splicing mutation was identified in a pediatric patient with two metachronous primary cancers that are constituent tumors of the Li-Fraumeni syndrome. Genomic DNA from the second tumor showed 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 heterozygous state, predominantly normal mRNA was expressed and the mutant p53 protein 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 proves a more general pattern of expression of mutant p53 in individuals with germline mutations, these findings may explain the paucity of tumors in individuals affected with the Li-Fraumeni syndrome.
authors: Department of Pediatrics, Children's Hospital of Philadelphia, Pennsylvania 19104.
authors: C A
authors: CA
authors: Felix
authors: E A
authors: EA
authors: Strauss
authors: D
authors: D
authors: D'Amico
authors: M
authors: M
authors: Tsokos
authors: S
authors: S
authors: Winter
authors: T
authors: T
authors: Mitsudomi
authors: M M
authors: MM
authors: Nau
authors: D L
authors: DL
authors: Brown
authors: A M
authors: AM
authors: Leahey
authors: M E
authors: ME
authors: Horowitz
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D002648:Child; D016158:Genes, p53; D006801:Humans; D016864:Li-Fraumeni Syndrome / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016609:Neoplasms, Second Primary / Q000737:chemistry / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016159:Tumor Suppressor Protein p53