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

Abstract

BackgroundLittle 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.MethodsTP53 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.ResultsWe 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).ConclusionsThere 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.

Germline mutations in young non-smoking women with lung adenocarcinoma

“…These conditions are characterized by predisposition to a wide spectrum of neoplasia, including soft-tissue sarcoma, osteosarcoma, leukemia, breast cancer, brain tumors, and adrenocortical carcinoma, often at early age at onset. Although lung cancer is not a classic LFS spectrum cancer, it has been linked to LFS [19,36]. Preliminary data from the LIFESCREEN randomized clinical trial suggest that LUAD is indeed part of the spectrum, being the most frequent tumor in the LFS cohort under study [37].…”

“…A number of susceptibility loci and genes have been identified including 5p15 [8,9], 6p2 [10,11], 15q25.1 [10,11], EGFR [12][13][14], HER2 [15], BRCA [16], BAP1 [17], and PARK2 [18]. Also, germline TP53 and DICER1 mutations causing Li-Fraumeni and DICER1 syndromes, respectively, are linked to an increased risk of lung cancer [19,20].…”

Clinical Characteristics and Prognosis Associated with Multiple Primary Cancers in Breast Cancer Patients

“…The most common genetic disease of TP53 mutation is Li-Fraumeni syndrome, which is characterized by a relatively high incidence of multiple cancers. Park et al [ 23 ] evaluated 14 patients with Li-Fraumeni syndrome and found that six out of 11 women had breast cancer, and five of them had breast cancer and MPCs. Similarly, Mai et al [ 24 ] reported that among women with Li-Fraumeni syndrome, breast cancer occurs most frequently in women with germline TP53 mutations.…”

Familial Lung Cancer: A Brief History from the Earliest Work to the Most Recent Studies

“…Some causal germline variants have been identified in a small proportion of familial lung cancer pedigrees. Mutations in TP53 have long been known to cause Li-Fraumeni syndrome [ 82 ], which causes an increased risk of lung cancer, among other cancers. More recently, a de novo mutation in a tumor of a Li-Fraumeni patient was found to have a deleterious mutation in CHEK2 [ 83 ].…”