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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus

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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Figure 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.

Mentions: The mutations consisted of seven known mutations and two novel mutations in 14 unrelated Korean patients with 30 tumors. Six missense mutations (11/14, 79%), two frameshift deletions (2/14, 14%), and one nonsense mutation (1/14, 7%) were detected (Table 1). All mutations were distributed among exons 3 to 8; the DNA-binding domain (n=10) and transactivation domain (n=3) (Table 1). The most common mutation locations were exons 8 (n=5), 5 (n=3), and 3 (n=3) in TP53. The recurrent mutations were located at codons 31 (n=2; p.Val31Ile), 175 (n=3; p.Arg175His), and 273 [n=4; p.Arg273His (n=3), and p.Arg273Cys (n=1)] in TP53 (Fig. 1). Two novel frameshift mutations (p.Pro98Leufs*25 and p.Pro27Leufs*17) were identified (Table 1, Fig. 2).


Germline TP53 Mutation and Clinical Characteristics of Korean Patients With Li-Fraumeni Syndrome
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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940490&req=5

Figure 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.
Mentions: The mutations consisted of seven known mutations and two novel mutations in 14 unrelated Korean patients with 30 tumors. Six missense mutations (11/14, 79%), two frameshift deletions (2/14, 14%), and one nonsense mutation (1/14, 7%) were detected (Table 1). All mutations were distributed among exons 3 to 8; the DNA-binding domain (n=10) and transactivation domain (n=3) (Table 1). The most common mutation locations were exons 8 (n=5), 5 (n=3), and 3 (n=3) in TP53. The recurrent mutations were located at codons 31 (n=2; p.Val31Ile), 175 (n=3; p.Arg175His), and 273 [n=4; p.Arg273His (n=3), and p.Arg273Cys (n=1)] in TP53 (Fig. 1). Two novel frameshift mutations (p.Pro98Leufs*25 and p.Pro27Leufs*17) were identified (Table 1, Fig. 2).

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Related in: MedlinePlus