Germline TP53 Mutation and Clinical Characteristics of Korean Patients With Li-Fraumeni Syndrome

Ann Lab Med. 2016 Sep;36(5):463-8. doi: 10.3343/alm.2016.36.5.463.

Abstract

Background: Little is known of the mutation and tumor spectrum of Korean patients with Li-Fraumeni syndrome (LFS). Owing to the rarity of LFS, few cases have been reported in Korea thus far. This study aimed to retrospectively review the mutations and clinical characteristics of Korean patients with LFS.

Methods: TP53 mutation was screened in 89 unrelated individuals at the Samsung Medical Center in Korea, from 2004 to 2015. Six additional mutation carriers were obtained from the literature.

Results: We identified nine different mutations in 14 Korean patients (male to female ratio=0.3:1). Two such frameshift mutations (p.Pro98Leufs*25, p.Pro27Leufs*17) were novel. The recurrent mutations were located at codons 31 (n=2; p.Val31Ile), 175 (n=3; p.Arg175His), and 273 (n=4; p.Arg273His and p.Arg273Cys). The median age at the first tumor onset was 25 yr. Ten patients (71%) developed multiple primary tumors. A diverse spectrum of tumors was observed, including breast (n=6), osteosarcoma (n=4), brain (n=4), leukemia (n=2), stomach (n=2), thyroid (n=2), lung (n=2), skin (n=2), bladder (n=1), nasal cavity cancer (n=1), and adrenocortical carcinoma (n=1).

Conclusions: There was considerable heterogeneity in the TP53 mutations and tumor spectrum in Korean patients with LFS. Our results suggest shared and different LFS characteristics between Caucasian and Korean patients. This is the first report on the mutation spectrum and clinical characteristics from the largest series of Korean LFS patients.

Keywords: Germline mutation; Li-Fraumeni syndrome; TP53.

MeSH terms

  • Adolescent
  • Adult
  • Asian People / genetics
  • Base Sequence
  • Child
  • Child, Preschool
  • Codon
  • Female
  • Frameshift Mutation
  • Germ-Line Mutation
  • Humans
  • Infant
  • Li-Fraumeni Syndrome / genetics*
  • Li-Fraumeni Syndrome / pathology
  • Male
  • Middle Aged
  • Neoplasms, Multiple Primary
  • Polymorphism, Genetic
  • Republic of Korea
  • Retrospective Studies
  • Tumor Suppressor Protein p53 / genetics*
  • Young Adult

Substances

  • Codon
  • Tumor Suppressor Protein p53