Ann Lab Med.  2016 Sep;36(5):463-468. 10.3343/alm.2016.36.5.463.

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

• Park KJ
• Choi HJ
• Suh SP
• Ki CS
• Kim JW

• KMID: 2373577
• DOI: http://doi.org/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.

Keyword

Li-Fraumeni syndrome; TP53; Germline mutation

MeSH Terms

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

Figure

• 

  Fig. 1 Frequency distribution of TP53 germline mutations by codon. (A) Data reproduced from the International Agency for Research on Cancer (IARC) TP53 database (version R18, April 2016, http://p53.iarc.fr/) [7]. (B) Data from Korean patients with Li-Fraumeni syndrome. Figures above the vertical line represent the codon locations of the mutations.

• 

  Fig. 2 Sequence chromatogram of two novel frameshift mutations in TP53. (A) Heterozygous mutation of c.293delC (p.Pro98Leufs*25) identified in patient 6, who was treated for adrenocortical carcinoma, osteosarcoma, brain cancer, and therapy-related neoplasm. (B) Heterozygous mutation of c.78delT (p.Pro27Leufs*17) identified in patient 7 with multiple primary tumors comprising left breast cancer (28 yr), neurofibroma (33 yr), right breast cancer (38 yr), right nasal cavity squamous cell carcinoma (38 yr), and lung adenocarcinoma (43 yr). Forward and reverse sequences are shown at the top and bottom, respectively.

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