Li-Fraumeni Syndrome

Rare autosomal dominant syndrome characterized by mesenchymal and epithelial neoplasms at multiple sites. MUTATION of the p53 tumor suppressor gene, a component of the DNA DAMAGE response pathway, apparently predisposes family members who inherit it to develop certain cancers. The spectrum of cancers in the syndrome was shown to include, in addition to BREAST CANCER and soft tissue sarcomas (SARCOMA); BRAIN TUMORS; OSTEOSARCOMA; LEUKEMIA; and ADRENOCORTICAL CARCINOMA.

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Networked: 182 relevant articles (2 outcomes, 6 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Neoplasms (Cancer)
2.	Breast Neoplasms (Breast Cancer)
3.	Stomach Neoplasms (Stomach Cancer)
4.	Peutz-Jeghers Syndrome (Polyposis, Hamartomatous Intestinal)
5.	Multiple Hamartoma Syndrome (Cowden's Disease)

Experts

1.	Savage, Sharon A: 5 articles (01/2022 - 01/2017)
2.	Dannenberg, Andrew J: 4 articles (01/2020 - 03/2014)
3.	Herbert, Brittney-Shea: 4 articles (01/2020 - 03/2014)
4.	Subbaramaiah, Kotha: 4 articles (01/2020 - 03/2014)
5.	Strong, Louise C: 4 articles (10/2017 - 03/2013)
6.	Malkin, David: 4 articles (01/2017 - 06/2012)
7.	Khincha, Payal P: 3 articles (01/2022 - 12/2017)
8.	Hwang, Paul M: 3 articles (01/2021 - 03/2013)
9.	Wang, Ping-Yuan: 3 articles (01/2021 - 03/2013)
10.	Mai, Phuong L: 3 articles (12/2020 - 01/2017)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Li-Fraumeni Syndrome:

1.	Codon (Codons)IBA 09/01/1999 - "P16INK4A codon 94 mutation observed in our family is a novel mutation in Li-Fraumeni syndrome. " 09/01/1999 - "Hereditary TP53 codon 292 and somatic P16INK4A codon 94 mutations in a Li-Fraumeni syndrome family." 08/06/1998 - "We report that Li-Fraumeni syndrome (LFS) fibroblast strains heterozygous for TP53 mutation at either codon 245 or 234 exhibit markedly reduced or no expression of p21WAF1 following UV irradiation, respectively. " 01/01/1997 - "A missense mutation at codon 265 of TP53 was found in three patients of a family that complied with the definition of the Li-Fraumeni syndrome. " 06/06/1996 - "We report details of a family with classic Li-Fraumeni syndrome in which there is a mutation in codon 344 of the tumour suppressor gene TP53. "
2.	cytidylyl-(3'-5')-cytidine (CpC)IBA 11/01/2017 - "Our strategy may be effective in managing other patients with recurrent CPC and Li-Fraumeni syndrome." 09/01/2008 - "Although both tumour types are associated with Li-Fraumeni syndrome (LFS), the penetrance of germline TP53 mutations in CPC remains to be established. " 01/01/2005 - "The authors report the successful treatment of a 2-year-old patient with widely disseminated CPC and Li-Fraumeni syndrome. " 11/01/2017 - "Here, we discuss a 3-year-old girl with CPC and Li-Fraumeni syndrome who achieved full remission after surgery and chemotherapy, with radiation therapy spared. " 01/01/2023 - "The CPC tumor had only a pathogenic germline TP53 variant, based on American College of Medical Genetics (ACMG) criteria, with a clinical and familiar history of Li-Fraumeni syndrome. "
3.	Valine (L-Valine)FDA Link 02/01/1992 - "One pedigree was consistent with the Li-Fraumeni syndrome, and bone marrow from both diagnosis and remission indicated a germline G to T transversion at codon 272 (valine to leucine). "
4.	Leucine (L-Leucine)FDA Link 02/01/1992 - "One pedigree was consistent with the Li-Fraumeni syndrome, and bone marrow from both diagnosis and remission indicated a germline G to T transversion at codon 272 (valine to leucine). "
5.	Proteins (Proteins, Gene)FDA Link 10/01/2002 - "Furthermore, regulated expression of wild-type p53 in p53 null Li-Fraumeni syndrome human fibroblasts significantly augmented the expression of XPC protein. " 09/01/1993 - "Here we report the biochemical characteristics of several Li-Fraumeni syndrome associated mutant p53 proteins in order to assess the influence of germ-line mutant p53 on the functions of the wild-type p53. " 10/01/2022 - "Li-Fraumeni syndrome is a multiple cancer syndrome caused by germline alterations of the tumor protein 53 (TP53) tumor suppressor gene and is often associated with ACC. " 01/01/2022 - "Malignant gliomas, IDH wild-type, arising in patients with Li-Fraumeni syndrome typically show somatic mutations of TP53 as well as complex copy number alterations, but little is known about the loss of SMARCB1 or SMARCA4 protein expression in this context. " 01/01/2022 - "Li-Fraumeni syndrome (LFS) is a cancer-prone, autosomal dominant syndrome caused by underlying germline gene mutations of TP53, a tumor-suppressor gene encoding the p53 protein with a major role in apoptosis, DNA repair and cell cycle regulation. "
6.	DNA (Deoxyribonucleic Acid)IBA 04/02/2007 - "Studies indicate that p53 missense mutations in the DNA-binding domain identical with those inherited in the Li-Fraumeni syndrome, have distinct properties. " 02/15/2001 - "Mechanism of functional inactivation of a Li-Fraumeni syndrome p53 that has a mutation outside of the DNA-binding domain." 01/01/2001 - "Furthermore, p53 was screened from blood DNA (exons 2-11) with temporal temperature gradient electrophoresis (TTGE) since germline mutations in p53 are seen in Li-Fraumeni syndrome. " 06/01/1998 - "The resulting two-dimensional gene scanning (TDGS) test was evaluated by screening, in a blinded fashion, 29 coded DNA samples from Li-Fraumeni syndrome patients with previously identified germline mutations. " 11/01/1994 - "A germline 2.35 kb deletion of p53 genomic DNA creating a specific loss of the oligomerization domain inherited in a Li-Fraumeni syndrome family."
7.	NucleotidesIBA 05/01/1999 - "The comparative analysis of the frequencies of nucleotide exchanges in mutational spectra of gene p53 (5-8 exons) between germline cancer-prone families (Li-Fraumeni syndrome), between somatic mutations in the tumors of different histogenesis and cell lines, obtained from them, was carried out. " 12/01/2001 - "A hCHK2/hCds1 polymorphism in codon 84 (A-->G at nucleotide 252) was recently identified in Li-Fraumeni syndrome patients. " 12/17/2009 - "We report herein on Li Fraumeni syndrome in a family whose members are carriers of a novel TP53 gene mutation at exon 4. The mutation comprises an insertion/duplication of seven nucleotides affecting codon 110 and generating a new nucleotide sequence and a premature stop codon at position 150. " 01/01/1998 - "The database describes each p53 mutation (type of the mutation, exon and codon affected by the mutation, nucleotide and amino acid change), each family (family history of cancer, diagnosis of Li-Fraumeni syndrome), each affected individual (sex, generation, p53 status, from which parent the mutation was inherited) and each tumour (type, age of onset, p53 status-loss of heterozygosity, immunostaining). " 04/14/2000 - "In this study, we have analyzed the damage induction at nucleotide resolution by ligase-mediated polymerase chain reaction and compared the repair of ultraviolet radiation-induced cyclobutane pyrimidine dimers within exon 8 of p53 gene in normal and Li-Fraumeni syndrome fibroblasts as well as in normal and human papillomavirus 16 E6 and E7 protein-expressing human mammary epithelial cells. "
8.	Intercellular Signaling Peptides and Proteins (Growth Factors)IBA 06/01/1995 - "This study suggests that progression towards a glioblastoma in both the general population and in patients with Li-Fraumeni syndrome may involve potential autocrine and paracrine stimulation by growth factors such as PDGF." 01/01/2000 - "Chronic exposure to growth factors (insulin-like growth factor-I in acromegaly), mutations in tumour suppressor genes (TP53 in Li Fraumeni syndrome) and long-term exposure to immunosuppressive agents (cyclosporin A) may also give rise to similar environments and are associated with the development of a range of solid tumours. "
9.	RNA (Ribonucleic Acid)IBA 01/01/2017 - "Based on our platform, we were able to obtain novel insights into post-transcriptional regulation, such as the putative association between CPSF6 binding, RNA structural domains, and Li-Fraumeni syndrome SNPs. " 05/01/1992 - "The studies reported here focus on the analysis of the expression of normal and mutant p53 RNA and protein in germline configuration and demonstrate that normal skin fibroblasts derived from members of a family with Li-Fraumeni syndrome express mutant p53Gly----Asp(245) protein and RNA at levels similar to the wild-type p53. "
10.	Pyrimidine DimersIBA 10/31/1997 - "We have shown previously that Li-Fraumeni syndrome fibroblasts homozygous for p53 mutations are deficient in the removal of UV-induced cyclobutane pyrimidine dimers from genomic DNA, but still proficient in the transcription-coupled repair pathway (Ford, J. " 04/14/2000 - "In this study, we have analyzed the damage induction at nucleotide resolution by ligase-mediated polymerase chain reaction and compared the repair of ultraviolet radiation-induced cyclobutane pyrimidine dimers within exon 8 of p53 gene in normal and Li-Fraumeni syndrome fibroblasts as well as in normal and human papillomavirus 16 E6 and E7 protein-expressing human mammary epithelial cells. "

Therapies and Procedures

1.	Radiotherapy 01/01/2019 - "For PV carriers in high-penetrance genes like BRCA1, BRCA2, and TP53, prophylactic mastectomy is often recommended and radiation therapy avoided when possible for those with Li-Fraumeni syndrome (LFS). " 11/01/2020 - "Radiation therapy and secondary malignancy in Li-Fraumeni syndrome: A hereditary cancer registry study." 11/24/2022 - "The Role of Radiation Therapy in Locally Advanced Breast Cancer in a Patient With Li-Fraumeni Syndrome." 01/01/2022 - "Breast Cancer after Radiation Therapy in a Patient with Li-Fraumeni Syndrome: A Case Report." 10/01/2020 - "Li-Fraumeni syndrome (LFS) is a genetic disease that is hypersensitive to radiotherapy. "
2.	Drug Therapy (Chemotherapy) 08/01/2014 - "We report the case of a young, never-smoker woman with Li-Fraumeni syndrome and advanced lung adenocarcinoma refractory to multiple lines of conventional chemotherapy and negative for actionable alterations by routine testing. " 01/01/2021 - "Choroid plexus carcinomas associated with Li-Fraumeni syndrome are less responsive to chemotherapy, and there is a need to avoid radiation therapy leading to poorer outcomes and survival. " 01/01/2018 - "An analysis of the literature and the clinical case indicate the success of multiple surgical interventions and chemotherapy courses performed for a long time in the patient with Li-Fraumeni syndrome manifested by colon adenocarcinoma, recurrent B-cell lymphoma, and multiple anaplastic oligodendroglioma of the brain. " 11/01/2017 - "Here, we discuss a 3-year-old girl with CPC and Li-Fraumeni syndrome who achieved full remission after surgery and chemotherapy, with radiation therapy spared. " 10/02/2012 - "Li-Fraumeni syndrome with simultaneous osteosarcoma and liver cancer: increased expression of a CD44 variant isoform after chemotherapy."
3.	Therapeutics 05/01/2007 - "p53 therapy in a patient with Li-Fraumeni syndrome." 09/01/2023 - "We report an advanced urothelial cancer in a patient with Li-Fraumeni syndrome who demonstrated good efficacies to sequential medical therapy." 09/01/2023 - "A case of sequential medical therapy for advanced ureteral cancer in Li-Fraumeni syndrome." 12/01/2017 - "Participants included 116 individuals with Li-Fraumeni syndrome with a germline TP53 pathogenic variant who were aged 3 years or older at the time of baseline screening and had not received active cancer therapy at least 6 months prior to screening. " 10/01/2017 - "Li-Fraumeni Syndrome Disease Model: A Platform to Develop Precision Cancer Therapy Targeting Oncogenic p53."
4.	Proton Therapy 04/18/2022 - "We present a case of a patient with Li-Fraumeni Syndrome who developed acute onset pericarditis, presumed to be secondary to proton beam therapy." 10/01/2020 - "Re-irradiation using proton therapy for radiation-induced secondary cancer with Li-Fraumeni syndrome: A case report and review of literature."
5.	Breast Implants (Breast Implant) 01/01/2019 - "Increasing Evidence for the Association of Breast Implant-Associated Anaplastic Large Cell Lymphoma and Li Fraumeni Syndrome." 12/01/2015 - "Breast implant-associated anaplastic large cell lymphoma in a patient with Li-Fraumeni syndrome." 01/01/2019 - "We report a case of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) occurring in a 53-year-old female with Li Fraumeni syndrome (LFS) with a prior history of breast cancer. "