Li-Fraumeni syndrome(LFS) is an autosomal dominant disorder that predisposes individuals to multiple forms of cancer including breast cancer, soft tissue sarcoma, brain tumor, osteosarcoma, leukemia, and adrenocortical carcinoma. Recently, germ-line mutation of the p53 tumor suppressor gene has been implicated in this familial disorder. We report a case of a 25-year old woman who presented with bilateral breast cancer and uterine leiomyoma. Her mother had died of early-onset bilateral breast cancer. And her younger sister had breast carcinoma as well, which was identified at the age of 22, indicating her strong familial history. To test for the presence of the p53 germ-line mutation, we analyzed the genomic DNA from the peripheral blood of the proband and her sister by PCR-SSCP analysis of exon 5 through exon 8 of the p53 gene. As a result, a p53 mutation in exon 7 was detected in an allele, and it was shared with her sister as the same pattern. Sequencing analysis determined the altered nucleotide at codon 248(CGG < TGG) which is one of the most frequent mutation sites related to LFS. Therefore, this patient has the most consistent characteristic features of LFS phenotype and it is believed that this case is the first report of a family with Li-Fraumeni syndrome carrying the p53 germ-line mutation in Korea.
Adult ; Base Sequence ; Breast Neoplasms/diagnosis/genetics ; Case Report ; Female ; Genes, p53 ; Germ-Line Mutation ; Human ; Korea ; Li-Fraumeni Syndrome/*diagnosis/genetics ; Molecular Sequence Data ; Pedigree ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Sequence Analysis, DNA ; Support, Non-U.S. Gov't

This erratum is being published to correct the printing error on page 286 of the article entitled 'Panton-Valentine leukocidin positive Staphylococcus aureus isolated from blood in Korea' by Kim JS, Park JS, Song W, Kim HS, Cho HC, Lee KM, Kim EC in Korean J Lab Med 2007;27:286-91. DOI 10.3343/kjlm. 2007.27.4.286 as follows. The heading of the right column of the Table 1 was misprinted as methicillin-resistant, so it should be corrected to methicillin-susceptible.
Adult ; Amino Acid Substitution ; Brain Neoplasms/radiotherapy/surgery ; Breast Neoplasms/diagnosis/radiotherapy/surgery ; Female ; *Genetic Counseling ; Genetic Predisposition to Disease ; *Germ-Line Mutation ; Humans ; Li-Fraumeni Syndrome/*diagnosis/genetics/therapy ; Mutation, Missense ; Pedigree ; Tumor Suppressor Protein p53/*genetics

We report a 26-yr-old female patient with bilateral breast cancer who was clinically diagnosed with Li-Fraumeni like syndrome (LFL) and subsequently found to have a germline mutation of the TP53 gene. The patient was initially diagnosed with right breast cancer at age 24 yr and then with left breast cancer at age 25 yr. Surgery and radiotherapy were performed accordingly. The patient had a family history of various types of early onset cancers and was referred to a genetic counseling clinic. She was clinically diagnosed with LFL. Genetic analysis of the TP53 tumor suppressor gene was performed with the patient's consent. Direct sequencing of TP53 gene exons 5, 6, 8, 9, and 11 revealed a ermline missense mutation, resulting in an amino acid change from an arginine to a histidine (g.13203G>A, p.R175H). Considering the family history, individualized cancer surveillance was performed including a gastroscopy and a brain MRI. Even though the patient had not shown any neurological symptoms, a huge mass on the temporal lobe was incidentally found and the patient received surgery and radiotherapy. Although the residual mass required further treatment, the patient decided on supportive care alone and was discharged. We report a case of LFL, with a germline TP53 mutation, which was confirmed by gene sequencing in Korea. This case shows how genetic predisposition screening and counseling in patients, suspected of having a familial cancer syndrome, can influence the course of the patient.
Adult ; Amino Acid Substitution ; Brain Neoplasms/radiotherapy/surgery ; Breast Neoplasms/diagnosis/radiotherapy/surgery ; Female ; *Genetic Counseling ; Genetic Predisposition to Disease ; *Germ-Line Mutation ; Humans ; Li-Fraumeni Syndrome/*diagnosis/genetics/therapy ; Mutation, Missense ; Pedigree ; Tumor Suppressor Protein p53/*genetics

Li-Fraumeni syndrome (LFS) is a rare, inherited syndrome associated with increased risk of various early-onset tumors. Since the introduction of classic LFS criteria, various criteria have been proposed to include patients with incomplete LFS features, which make up Li-Fraumeni-like syndromes (LFL). Germline missense mutations of TP53 are the primary cause of LFS and LFL. Mutations mostly reside in the DNA-binding domain of the gene and have a dominant-negative effect (DNE) over alternate wild-type alleles. Germline TP53 mutation c.566C>T results in the missense mutation GCC (Ala) to GTC (Val) at codon 189 (A189V) and has been reported in a case of multiple primary colon tumors. Herein we report a second case of the same mutation in a breast cancer patient, who has familial history of late-onset malignancies. Due to the relatively late onset of malignancies, neither case fulfils previously defined criteria for the syndrome. Mutational analysis for breast tissue in this patient showed a loss of heterozygosity. These clinical features may suggest a relatively weak DNE of A189V compared to other TP53 mutations, and in silico predictions and in vitro findings of the function of A189V mutant protein are conflicting. Considering the increased risk of malignancies and the therapeutic implications for patients who have a TP53 mutation, care must be taken when treating those who are suspected of possessing cancer-prone traits due to TP53 mutation, especially when there is a family history of late-onset cancer with low penetrance.
Adolescent ; Adult ; Breast Neoplasms/complications/*diagnosis/therapy ; Combined Modality Therapy ; Exons ; Female ; Genotype ; Heterozygote ; Humans ; Li-Fraumeni Syndrome/complications/*diagnosis/therapy ; Middle Aged ; Multimodal Imaging ; Mutation, Missense ; Pedigree ; Sequence Analysis, DNA ; Tumor Suppressor Protein p53/genetics ; Young Adult

Li-Fraumeni syndrome (LFS) is a rare, inherited syndrome associated with increased risk of various early-onset tumors. Since the introduction of classic LFS criteria, various criteria have been proposed to include patients with incomplete LFS features, which make up Li-Fraumeni-like syndromes (LFL). Germline missense mutations of TP53 are the primary cause of LFS and LFL. Mutations mostly reside in the DNA-binding domain of the gene and have a dominant-negative effect (DNE) over alternate wild-type alleles. Germline TP53 mutation c.566C>T results in the missense mutation GCC (Ala) to GTC (Val) at codon 189 (A189V) and has been reported in a case of multiple primary colon tumors. Herein we report a second case of the same mutation in a breast cancer patient, who has familial history of late-onset malignancies. Due to the relatively late onset of malignancies, neither case fulfils previously defined criteria for the syndrome. Mutational analysis for breast tissue in this patient showed a loss of heterozygosity. These clinical features may suggest a relatively weak DNE of A189V compared to other TP53 mutations, and in silico predictions and in vitro findings of the function of A189V mutant protein are conflicting. Considering the increased risk of malignancies and the therapeutic implications for patients who have a TP53 mutation, care must be taken when treating those who are suspected of possessing cancer-prone traits due to TP53 mutation, especially when there is a family history of late-onset cancer with low penetrance.
Adolescent ; Adult ; Breast Neoplasms/complications/*diagnosis/therapy ; Combined Modality Therapy ; Exons ; Female ; Genotype ; Heterozygote ; Humans ; Li-Fraumeni Syndrome/complications/*diagnosis/therapy ; Middle Aged ; Multimodal Imaging ; Mutation, Missense ; Pedigree ; Sequence Analysis, DNA ; Tumor Suppressor Protein p53/genetics ; Young Adult