title: Functional studies of a novel germline p53 splicing mutation identified in a patient with Li-Fraumeni-like syndrome.
abstract: Most p53 mutations identified in Li-Fraumeni syndrome (LFS) are missense mutations; splicing mutations have rarely been reported. A novel splicing p53 mutation was identified in a patient with Li-Fraumeni-like syndrome (LFL). Usually, p53 missense mutants identified in LFS and cancer cells function as dominant negative mutations interfering with wild-type p53 function. However, the mechanism by which p53 haploinsufficiency causes carcinogenesis is not well characterized. In this study, we describe a novel splicing mutation that results in the loss-of-function of p53. These findings suggest a linkage between the loss-of-function type p53 mutation and a LFL phenotype.
authors.affiliation: Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Piao
authors.forename: Naoto
authors.initials: N
authors.lastname: Sakurai
authors.forename: Shotaro
authors.initials: S
authors.lastname: Iwamoto
authors.forename: Junji
authors.initials: J
authors.lastname: Nishioka
authors.forename: Kaname
authors.initials: K
authors.lastname: Nakatani
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Komada
authors.forename: Shuki
authors.initials: S
authors.lastname: Mizutani
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takagi
mesh_terms: D000293:Adolescent; D000818:Animals; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D017931:DNA Primers; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D016864:Li-Fraumeni Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments; D010641:Phenotype; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D017931:DNA Primers; D010446:Peptide Fragments; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D008156:Luciferases