title: Novel p53 splice site mutations in three families with Li-Fraumeni syndrome.
abstract: Germline mutations in the p53 tumor suppressor gene predispose to a variety of cancers in families with Li-Fraumeni syndrome. Most germline p53 mutations observed to date cause amino acid substitutions in the protein's central sequence-specific DNA binding domain. Outside this conserved core region, however, we found novel alterations in sequences that regulate precursor mRNA splicing in three Li-Fraumeni syndrome families. Two splice site mutations affected the consensus sequence at the splice donor sites of introns 1 and 9, and produced unstable variant transcripts in normal cells. A third mutation at the splice acceptor site of intron 9 generated splicing at a cryptic acceptor site in intron 9. These splice site alterations emphasize the need to examine both noncoding and untranslated regions of the p53 gene for germline mutations in Li-Fraumeni syndrome families. Oncogene (2000) 19, 4230 - 4235
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, MA 02115, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Verselis
authors.forename: J G
authors.initials: JG
authors.lastname: Rheinwald
authors.forename: J F
authors.initials: JF
authors.lastname: Fraumeni
authors.forename: F P
authors.initials: FP
authors.lastname: Li
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured / Q000378:metabolism; D003062:Codon / Q000235:genetics; D016384:Consensus Sequence; D004252:DNA Mutational Analysis; D005260:Female; D016158:Genes, p53; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D015603:Keratinocytes / Q000378:metabolism; D016864:Li-Fraumeni Syndrome / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D003062:Codon; D012333:RNA, Messenger