Functional studies of a novel germline p53 splicing mutation identified in a patient with Li-Fraumeni-like syndrome

Jinhua Piao; Naoto Sakurai; Shotaro Iwamoto; Junji Nishioka; Kaname Nakatani; Yoshihiro Komada; Shuki Mizutani; Masatoshi Takagi

doi:10.1002/mc.21912

Functional studies of a novel germline p53 splicing mutation identified in a patient with Li-Fraumeni-like syndrome

Mol Carcinog. 2013 Oct;52(10):770-6. doi: 10.1002/mc.21912. Epub 2012 Apr 11.

Authors

Jinhua Piao¹, Naoto Sakurai, Shotaro Iwamoto, Junji Nishioka, Kaname Nakatani, Yoshihiro Komada, Shuki Mizutani, Masatoshi Takagi

Affiliation

¹ Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.

PMID: 22495821
DOI: 10.1002/mc.21912

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.

Keywords: Li-Fraumeni-like syndrome; p53; splicing mutation.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Animals
Blotting, Western
Bone Neoplasms / genetics
Bone Neoplasms / metabolism
Bone Neoplasms / pathology
Breast Neoplasms / genetics*
Breast Neoplasms / metabolism
Breast Neoplasms / pathology
Cell Differentiation
Cell Proliferation
Cells, Cultured
DNA Primers
Embryo, Mammalian / cytology
Embryo, Mammalian / metabolism
Female
Fibroblasts / cytology
Fibroblasts / metabolism
Genetic Predisposition to Disease
Germ-Line Mutation / genetics*
Humans
Immunoenzyme Techniques
Immunoprecipitation
Li-Fraumeni Syndrome / genetics*
Li-Fraumeni Syndrome / metabolism
Li-Fraumeni Syndrome / pathology
Luciferases / metabolism
Mice
Mice, Knockout
Osteosarcoma / genetics*
Osteosarcoma / metabolism
Osteosarcoma / pathology
Peptide Fragments
Phenotype
RNA Splicing / genetics*
RNA, Messenger / genetics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Tumor Suppressor Protein p53 / genetics*
Tumor Suppressor Protein p53 / metabolism

Substances

DNA Primers
Peptide Fragments
RNA, Messenger
TP53 protein, human
Tumor Suppressor Protein p53
Luciferases