Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome, with the characteristics of early onset of cancer and high cancer incidence. TP53 is widely accepted as a pathogenic gene of LFS. A 2 years and 6 months old boy is reported in this article, who was diagnosed with embryonal rhabdomyosarcoma (RMS) in the left submandibular region. His brother died of RMS, and his grandmother was diagnosed with breast cancer. TP53 gene mutation detection was performed in this patient and some family members, indicating a missense mutation in exon 8 of the patient: c.844C>T (p.Arg282Trp, heterozygous). TP53 mutation was also found in his mother and sister. The boy met the diagnostic criteria for LFS. Among pediatric patients, the most common LFS diseases include osteosarcoma, adrenocortical cancer, central nervous system tumor, and soft tissue tumor. Additionally, leukemia and lymphoma are also involved. LFS patients have a high risk to suffer secondary or even multiple cancers. Therefore, it is necessary to perform genetic detection for pediatric cancer patients, especially those with hereditary predisposition cancers. TP53 mutation often indicates poor prognosis, so it is important to take active treatment and systematic monitoring for LFS family.
Child, Preschool ; Genes, p53 ; Humans ; Li-Fraumeni Syndrome ; genetics ; Male ; Mutation ; Rhabdomyosarcoma ; genetics

Germline mutations in cancer causing genes result in high risk of developing cancer throughout life. These cancer predisposition syndromes (CPS) are especially prevalent in childhood brain tumors and impact both the patient's and other family members' survival. Knowledge of specific CPS may alter the management of the cancer, offer novel targeted therapies which may improve survival for these patients, and enables early detection of other malignancies. This review focuses on the role of CPS in pediatric high grade gliomas (PHGG), the deadliest group of childhood brain tumors. Genetic aspects and clinical features are depicted, allowing clinicians to identify and diagnose these syndromes. Challenges in the management of PHGG in the context of each CPS and the promise of innovative options of treatment and surveillance guidelines are discussed with the hope of improving outcome for individuals with these devastating syndromes.
Brain Neoplasms ; Germ-Line Mutation ; Glioma ; Hope ; Humans ; Li-Fraumeni Syndrome ; Neurofibromatosis 1

Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary disorder characterised by a variety of different tumor types in children and young adults. That contains with a germline mutation in the tumor suppressor gene Tumor Protein p53 (TP53). That is extremely rare. Furthermore, this is sometimes overlooked. Here, we report a case of LFS which was confirmed by mutational analysis of the p53 gene. Also, literature review is intended to improve understanding of this disease entity.
Adenocarcinoma* ; Child ; Genes, p53 ; Genes, Tumor Suppressor ; Germ-Line Mutation ; Humans ; Li-Fraumeni Syndrome* ; Lung* ; Osteosarcoma* ; Young Adult

Genes, p53 ; Genetic Predisposition to Disease ; Germ-Line Mutation ; Humans ; Li-Fraumeni Syndrome/genetics* ; Tumor Suppressor Protein p53/genetics*

Osteosarcoma is a primary malignant bone tumor that accounts for 5% of childhood cancers. Despite the use of chemotherapy, long-term survival has reached a plateau, and this figure has not changed for almost 20 years. Therefore, there is a need for understanding of the basic biology and pathogenesis of osteosarcoma in order to develop more therapeutic strategies and ultimately improve survival. This article reviews current state of knowledge about several aspects of osteosarcoma biology with regard to host genetic predispositions, cytogenetics and molecular markers. Genetic conditions with a predisposition to osteosarcoma include hereditary retinoblastoma, Li-Fraumeni syndrome, Rothmund-Thomson syndrome and Werner syndrome. Although most of osteosarcomas are sporadic, these syndromes may provide important clues to the pathogenesis of sporadic osteosarcomas. A multitude of cytogenetic abnormalities have been detected, but no specific abnormalities that can serve as markers of osteosarcoma have been found. Areas of molecular aberrations include tumor suppressor pathway (RB and p53), oncogenes (Her-2), telomere maintenance, angiogenesis (VEGF), chemokines (CXCR4), cytoskeletons (Ezrin), matrix metalloproteinases and adhesion molecules (CD44). Understanding the contributions of the different cytogenetic and molecular aberrations will aid in discovering predictors of outcome and in devising therapies for osteosarcoma.
Biomarkers* ; Biology ; Chemokines ; Chromosome Aberrations ; Cytogenetics ; Cytoskeleton ; Drug Therapy ; Genetic Predisposition to Disease ; Li-Fraumeni Syndrome ; Matrix Metalloproteinases ; Oncogenes ; Osteosarcoma* ; Retinoblastoma ; Rothmund-Thomson Syndrome ; Telomere ; Werner Syndrome

Hereditary cancer syndrome is a genetic condition that causes and increases the risk for specific type of cancers. Recent advances in genetics have identified a number of genes associated with inherited susceptibility to cancer, and this rapid development of knowledge about cancer genetics have implications for all aspects of cancer management, including prevention, screening, and treatment. Hereditary patterns of cancer are often characterized by early age at onset, high penetrance, bilaterality in paired organs, vertical transmission through either parent, and an association with other types of tumors. Most representative hereditary cancer syndromes in gynecologic field are hereditary breast/ovarian cancer syndrome (HBOC), hereditary non-polyposis colorectal cancer (HNPCC), Li-Fraumeni syndrome, and Cowden syndrome. Several familial mutations of specific genes, such as BRCA1, 2, TP53, PTEN, MMR, CHEK2, are linked to hereditary cancer syndrome, which are responsible for hereditary gynecologic cancers. It would be very important for gynecologic doctors to know the inclusion criteria for the genetic assessment, taking family history, clinical evaluation, genetic testing, screening guideline and risk reduction strategies for women with hereditary high risk factor. The morbidity and mortality of gynecologic malignancies related to these syndromes could be reduced by the adequate clinical approach, although recent guidelines were developed with an acute awareness of the preliminary nature of much of our knowledge regarding the clinical application of the rapidly emerging field of molecular genetics, and with an appreciation for the need for flexibility when applying these guidelines to individual families.
Colorectal Neoplasms ; Female ; Genetic Testing ; Gynecology ; Hamartoma Syndrome, Multiple ; Humans ; Li-Fraumeni Syndrome ; Mass Screening ; Molecular Biology ; Neoplastic Syndromes, Hereditary ; Parents ; Penetrance ; Pliability ; Risk Factors ; Risk Reduction Behavior

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 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

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