title: A novel germ line p53 mutation in intron 6 in diverse childhood malignancies.
abstract: Screening for p53 mutations in exons 5 to 8 in 124 pediatric malignancies identified 18 abnormal shifts using single strand conformation polymorphism: 12 were missense mutations and in 6, no mutation was detected in the exon or in the splice donor acceptor sequences. Sequencing was then performed in the adjacent introns, revealing a G to A base substitution at 39 base pairs upstream to exon 7. This mutation was identified in the germ line of five of the patients, and also in the father of one, whose parents were available. For comparison, of the 184 normal controls similarly screened, only one had this mutation (P=0.036). Positive staining of p53 protein was observed in three of the paraffin embedded tissues that were available: brain tumor, rhabdomyosarcoma, and lymphocytes from a normal lymph node from the rhabdomyosarcoma patient. All tumors with the identified intron mutation were Li-Fraumeni syndrome tumors. Sequencing of all exons including splice sites was performed and revealed no mutation. We suggest that this mutation in intron 6 of the p53 gene stabilizes the wild type p53 protein, resulting in its abnormal accumulation. Mutations in the noncoding region of p53 should be further studied.
authors.affiliation: Cancer Molecular Genetics, Pediatric Hematology Oncology, Schneider Children's Medical Center of Israel, Petah Tiqva.
authors.forename: S
authors.initials: S
authors.lastname: Avigad
authors.forename: D
authors.initials: D
authors.lastname: Barel
authors.forename: O
authors.initials: O
authors.lastname: Blau
authors.forename: A
authors.initials: A
authors.lastname: Malka
authors.forename: M
authors.initials: M
authors.lastname: Zoldan
authors.forename: C
authors.initials: C
authors.lastname: Mor
authors.forename: M
authors.initials: M
authors.lastname: Fogel
authors.forename: I J
authors.initials: IJ
authors.lastname: Cohen
authors.forename: B
authors.initials: B
authors.lastname: Stark
authors.forename: Y
authors.initials: Y
authors.lastname: Goshen
authors.forename: J
authors.initials: J
authors.lastname: Stein
authors.forename: R
authors.initials: R
authors.lastname: Zaizov
mesh_terms: D001932:Brain Neoplasms / Q000737:chemistry / Q000235:genetics; D002648:Child; D005091:Exons; D005260:Female; D016158:Genes, p53; D018095:Germ-Line Mutation; D006801:Humans; D007438:Introns; D016864:Li-Fraumeni Syndrome / Q000235:genetics* / Q000378:metabolism; D008198:Lymph Nodes / Q000737:chemistry; D008297:Male; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing; D012208:Rhabdomyosarcoma / Q000737:chemistry / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D016159:Tumor Suppressor Protein p53