1,290 results match your criteria Li-Fraumeni Syndrome


Mutation screening of TP53, CHEK2 and BRCA genes in patients at high risk for hereditary breast and ovarian cancer (HBOC) in Brazil.

Breast Cancer 2018 Dec 11. Epub 2018 Dec 11.

Universidade Federal de São João del Rei (UFSJ), 400 Sebastião Gonçalves Coelho Ave., Chanadour, Divinópolis, MG, 35501-296, Brazil.

Background: Few studies related to hereditary breast and ovarian cancer syndrome (HBOC) have been conducted in Brazil, and they are restricted to only small areas of the country. Here, we report the mutation profile of BRCA1/2, CHEK2 and TP53 genes in a cohort from Minas Gerais state.

Methods: These genes from 44 patients at high risk for HBOC were screened through high-resolution melting and/or sequencing. Read More

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December 2018

Updates on progress in cancer screening for children with hereditary cancer predisposition syndromes.

Authors:
Surya P Rednam

Curr Opin Pediatr 2018 Dec 10. Epub 2018 Dec 10.

Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA.

Purpose Of Review: A significant proportion of pediatric cancer occurs in children with hereditary cancer predisposition syndromes. Their survival may be significantly improved and/or late effects diminished through screening for their greatly elevated cancer risks. Here, an overview of new developments in the field of pediatric cancer surveillance is provided. Read More

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December 2018

[TP53 mutations and hematological malignancies].

Rinsho Ketsueki 2018 ;59(11):2468-2474

Department of Pediatrics, St. Luke's International Hospital.

TP53 is a tumor-suppressor gene, and it is the most commonly mutated somatic gene in human cancer. Germline TP53 mutations correlate with a hereditary predisposition to cancer. Comprehensive genetic analysis revealed the role of germline and somatic TP53 gene mutations in hematological malignancies. Read More

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January 2018

Identifying patients with genetic predisposition to acute myeloid leukemia.

Best Pract Res Clin Haematol 2018 Dec 25;31(4):373-378. Epub 2018 Sep 25.

Section of Hematology/Oncology, Department of Medicine, The University of Chicago Comprehensive Cancer Center, The University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL 60637, USA; Section of Hematology/Oncology, Department of Human Genetics, The University of Chicago Comprehensive Cancer Center, The University of Chicago, 5841 S. Maryland Avenue, MC 2115, Chicago, IL 60637, USA. Electronic address:

Germline syndromes in myeloid leukemias are being discovered increasingly in patients, and their identification is essential for proper medical management to yield positive health outcomes for patients and their families. There needs to be a greater appreciation of germline predisposition driving the development of hematologic malignancies within the field of myeloid malignancies. Characterization of the influence of germline mutations on the development of myeloid malignancies is ongoing by utilization of next generation sequencing data and prognostic panels. Read More

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December 2018
3 Reads

Bayesian estimation of a semiparametric recurrent event model with applications to the penetrance estimation of multiple primary cancers in Li-Fraumeni syndrome.

Biostatistics 2018 Nov 14. Epub 2018 Nov 14.

Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston, Pressler St, TX, USA.

A common phenomenon in cancer syndromes is for an individual to have multiple primary cancers (MPC) at different sites during his/her lifetime. Patients with Li-Fraumeni syndrome (LFS), a rare pediatric cancer syndrome mainly caused by germline TP53 mutations, are known to have a higher probability of developing a second primary cancer than those with other cancer syndromes. In this context, it is desirable to model the development of MPC to enable better clinical management of LFS. Read More

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November 2018
4 Reads

Whole-body magnetic resonance imaging (WB-MRI) in oncology: recommendations and key uses.

Radiol Med 2018 Nov 14. Epub 2018 Nov 14.

Department of Radiology, IEO, European Institute of Oncology IRCCS, Milan, Italy.

The past decade has witnessed a growing role and increasing use of whole-body magnetic resonance imaging (WB-MRI). Driving these successes are developments in both hardware and software that have reduced overall examination times and significantly improved MR imaging quality. In addition, radiologists and clinicians have continued to find promising new applications of this innovative imaging technique that brings together morphologic and functional characterization of tissues. Read More

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November 2018
1 Read

Low risk of invasive lobular carcinoma of the breast in carriers of BRCA1 (hereditary breast and ovarian cancer) and TP53 (Li-Fraumeni syndrome) germline mutations.

Breast J 2018 Nov 9. Epub 2018 Nov 9.

Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Villejuif, France.

Background: Invasive lobular carcinoma (ILC) of the breast has epidemiological, molecular and clinical specificities, and should likely be considered a unique entity. As for genetic susceptibility, CDH1 germline mutations predispose exclusively to ILC. Data are however scarce regarding ILC in women with BRCA1/2 (Hereditary Breast and Ovarian Cancer) and TP53 (Li-Fraumeni syndrome) germline mutations. Read More

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November 2018
9 Reads

[Genetic predisposition to childhood cancer].

Pathologe 2018 Nov 5. Epub 2018 Nov 5.

Institut für Humangenetik, Medizinische Hochschule Hannover, Carl-Neuberg-Straße 1, 30625, Hannover, Deutschland.

Tackling the topic of genetic predisposition to childhood cancer requires close co-operation between pathologists, pediatric oncologists, and human geneticists. It is not just about the precise diagnosis and the most effective treatment of the cancer, but also to prevent further cancerous diseases for those affected and also their family members. On the basis of examples such as Li-Fraumeni syndrome, constitutional mismatch repair deficiency (CMMRD), medullo- and neuroblastoma, as well as hematological neoplasias, we will discuss the criteria for tumor predisposition genetic syndromes, the relationship between somatic and germline variants, and the immediate clinical consequences. Read More

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November 2018
4 Reads

Oncogenic role of SFRP2 in p53-mutant osteosarcoma development via autocrine and paracrine mechanism.

Proc Natl Acad Sci U S A 2018 Nov 1;115(47):E11128-E11137. Epub 2018 Nov 1.

Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029;

Osteosarcoma (OS), the most common primary bone tumor, is highly metastatic with high chemotherapeutic resistance and poor survival rates. Using induced pluripotent stem cells (iPSCs) generated from Li-Fraumeni syndrome (LFS) patients, we investigate an oncogenic role of secreted frizzled-related protein 2 (SFRP2) in p53 mutation-associated OS development. Interestingly, we find that high SFRP2 expression in OS patient samples correlates with poor survival. Read More

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November 2018
3 Reads

Translating genomic risk into an early detection strategy for sarcoma.

Genes Chromosomes Cancer 2018 Nov 1. Epub 2018 Nov 1.

Cancer Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.

Sarcomas have a strong genetic etiology, and the study of families affected by sarcomas has informed much of what we now understand of modern cancer biology. The recent emergence of powerful genetic technologies has led to astonishing reductions in costs and increased throughput. In the clinic, these technologies are revealing a previously unappreciated and rich landscape of genetic cancer risk. Read More

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November 2018

Variable population prevalence estimates of germline TP53 variants: A gnomAD-based analysis.

Hum Mutat 2018 Oct 23. Epub 2018 Oct 23.

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.

Reports of variable cancer penetrance in Li-Fraumeni syndrome (LFS) have raised questions regarding the prevalence of pathogenic germline TP53 variants. We previously reported higher-than-expected population prevalence estimates in sequencing databases composed of individuals unselected for cancer history. This study aimed to expand and further evaluate the prevalence of pathogenic and likely pathogenic germline TP53 variants in the gnomAD dataset (version r2. Read More

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October 2018
4 Reads

Li-Fraumeni Syndrome.

Authors:
Wendy H Vogel

J Adv Pract Oncol 2017 Nov-Dec;8(7):742-746. Epub 2017 Nov 1.

Wellmont Cancer Institute, Kingsport, Tennessee.

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November 2017

[Diagnosis, surveillance, and management of familial leukemia].

Authors:
Hiroshi Moritake

Rinsho Ketsueki 2018;59(10):2290-2299

Division of Pediatrics, Department of Developmental and Urological-Reproductive Medicine, Faculty of Medicine, University of Miyazaki.

Recently, the modern technique of comprehensive genomic analysis has identified both somatic mutations originating from tumor cells and germline mutations as causative genes of inherited familial leukemias among which Fanconi anemia and Li-Fraumeni syndrome are well known. Pathogenic germline mutations occur in various pathways, affecting DNA repair, ribosome biogenesis, telomere biology, hematopoietic transcription factors, tumor suppressors, neutrophil development, and other critical cellular processes. The clinical manifestations of germline mutations present a wide phenotypic spectrum of patients displaying congenital anomalies, early-onset myelodysplastic syndrome, or no medical problems until the developing leukemia. Read More

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January 2018
4 Reads

Osteosarcoma in a Child Below 2 Years of Age: Case Report and Review of the Literature.

J Pediatr Hematol Oncol 2018 Oct 9. Epub 2018 Oct 9.

Paediatric Oncology, Royal Hobart Hospital, Tas, Hobart.

Background: Osteosarcoma in children below the age of 5 is extremely rare.

Observation: We report on a previously well 14-month-old male infant, who presented with a reluctance to weight-bear on his right leg and had an associated limp. Plain imaging and a magnetic resonance imaging scan demonstrated a lytic lesion in the right distal femur. Read More

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October 2018
5 Reads

Boosting care and knowledge about hereditary cancer: European Reference Network on Genetic Tumour Risk Syndromes.

Fam Cancer 2018 Oct 9. Epub 2018 Oct 9.

Department of Human Genetics, Radboud University Medical Center, P.O. box 9101, 6500 HB, Nijmegen, The Netherlands.

Approximately 27-36 million patients in Europe have one of the ~ 5.000-8.000 known rare diseases. Read More

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October 2018
2 Reads

Probable hereditary familial overlap syndrome with multiple synchronous lung tumors.

Lung Cancer 2018 Oct 28;124:279-282. Epub 2018 Aug 28.

Thoracic Oncology Unit and Laboratory of Personalized Medicine, Instituto Nacional de Cancerología (INCan), México City, Mexico.

Here we report a case of a young, never-smoker Hispanic woman with a hereditary familial overlap syndrome (Li-Fraumeni plus CDH1). The patient developed multiple synchronous primary lung adenocarcinomas related to Intra-Alveolar Tumor Spread (STAS) several years after the diagnosis of a locally advanced lower limb osteosarcoma. Comprehensive genomic profiling by next generation sequencing (NGS) was performed on 90 cancer-related genes over each lung lesion (including two nodules of acinar adenocarcinoma, one lepidic spread tumor and in the STAS area). Read More

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October 2018
1 Read

Earlier Colorectal Cancer Screening May Be Necessary In Patients With Li-Fraumeni Syndrome.

Gastroenterology 2018 Sep 19. Epub 2018 Sep 19.

Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

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September 2018
1 Read

Current review of TP53 pathogenic germline variants in breast cancer patients outside Li-Fraumeni syndrome.

Hum Mutat 2018 Dec 3;39(12):1764-1773. Epub 2018 Oct 3.

QIMR Berghofer Medical Research Institute, Herston, Brisbane, Australia.

Pathogenic germline variants in TP53 predispose carriers to the multi-cancer Li-Fraumeni syndrome (LFS). Widespread multigene panel testing is identifying TP53 pathogenic variants in breast cancer patients outside the strict clinical criteria recommended for LFS testing. We aimed to assess frequency and clinical implications of TP53 pathogenic variants in breast cancer cohorts ascertained outside LFS. Read More

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December 2018
10 Reads

A novel p.Gly187Arg TP53 variant appears to result in Li-Fraumeni syndrome.

Pediatr Hematol Oncol 2018 Sep 21:1-5. Epub 2018 Sep 21.

b School of Medicine , Renown Children's Hospital, University of Nevada, Reno , USA.

Li-Fraumeni syndrome is an autosomal dominant cancer syndrome characterized by pathogenic variants in the TP53 gene on chromosome 17. The most common cancers in Li-Fraumeni kindreds include sarcomas, breast cancer, brain tumors, and adrenocortical carcinoma. We report a 9-month-old male who was diagnosed with an adrenocortical tumor and later found to harbor a novel TP53 c. Read More

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September 2018
1 Read

Genetic counselling of young women with breast cancer for Li-Fraumeni syndrome: a nationwide survey on the experiences and attitudes of genetics professionals.

Fam Cancer 2018 Sep 20. Epub 2018 Sep 20.

Department of Genetics, University Medical Center Utrecht, PO Box 85090, 3508 AB, Utrecht, The Netherlands.

Germline TP53 mutations are associated with an increased risk of early-onset breast cancer. Traditionally, it was not standard practice to offer TP53 genetic testing due to the low mutation detection rate and limited options regarding preventive screening. Recent guidelines recommend that all women diagnosed with breast cancer before the age of 31, irrespective of family history, should be offered TP53 genetic testing. Read More

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September 2018

Diagnosis of Li-Fraumeni Syndrome: Differentiating TP53 germline mutations from clonal hematopoiesis: Results of the observational AGO-TR1 trial.

Hum Mutat 2018 Dec 3;39(12):2040-2046. Epub 2018 Oct 3.

Center for Hereditary Breast and Ovarian Cancer, Center for Integrated Oncology (CIO), Medical Faculty, University Hospital Cologne, Cologne, Germany.

The Li-Fraumeni cancer predisposition syndrome (LFS1) presents with a variety of tumor types and the TP53 gene is covered by most diagnostic cancer gene panels. We demonstrate that deleterious TP53 variants identified in blood-derived DNA of 523 patients with ovarian cancer (AGO-TR1 trial) were not causal for the patients' ovarian cancer in three out of six TP53-positive cases. In three out of six patients, deleterious TP53 mutations were identified with low variant fractions in blood-derived DNA but not in the tumor of the patient seeking advice. Read More

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December 2018
4 Reads

Pediatric Case of Li-Fraumeni Syndrome Complicated with Supratentorial Anaplastic Ependymoma.

World Neurosurg 2018 Dec 6;120:125-128. Epub 2018 Sep 6.

Division of Neurosurgery, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Tottori, Japan.

Background: Li-Fraumeni syndrome is a genetic disease that is caused by mutation of the tumor suppressor gene TP53. Patients with this syndrome may develop multiple malignant neoplasms including brain tumors. We herein report the first case of Li-Fraumeni syndrome in which development of supratentorial anaplastic ependymoma led to difficulty in terms of selecting the optimal postoperative therapeutic protocol. Read More

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December 2018
16 Reads

deficiency causes a wide tumor spectrum and increases embryonal rhabdomyosarcoma metastasis in zebrafish.

Elife 2018 09 7;7. Epub 2018 Sep 7.

Department of Pathology, Massachusetts General Hospital Research Institute, Boston, Massachusetts.

The tumor-suppressor gene is mutated in >50% of human tumors and Li-Fraumeni patients with germ line inactivation are predisposed to developing cancer. Here, we generated deleted zebrafish that spontaneously develop malignant peripheral nerve-sheath tumors, angiosarcomas, germ cell tumors, and an aggressive Natural Killer cell-like leukemia for which no animal model has been developed. Because the tp53 deletion was generated in syngeneic zebrafish, engraftment of fluorescent-labeled tumors could be dynamically visualized over time. Read More

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September 2018
2 Reads

Families' and health care professionals' attitudes towards Li-Fraumeni syndrome testing in children: A systematic review.

Clin Genet 2018 Sep 7. Epub 2018 Sep 7.

Hereditary Cancer Centre, Department of Oncology and Haematology, Prince of Wales Hospital, Randwick, New South Wales, Australia.

Li-Fraumeni syndrome (LFS) is a highly penetrant cancer predisposition syndrome caused by germline TP53 mutations. Genetic testing is not routinely offered in asymptomatic children at risk of the condition as the benefits are debatable and the attitudes of families and health care professionals (HCPs) may vary. This review assessed the attitudes of families and HCPs towards offering genetic testing to children for LFS, with a focus on perceived advantages and disadvantages and involvement of children in the decision-making process. Read More

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September 2018
1 Read

De Novo Mutations Activating Germline TP53 in an Inherited Bone-Marrow-Failure Syndrome.

Am J Hum Genet 2018 Sep 23;103(3):440-447. Epub 2018 Aug 23.

Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan. Electronic address:

Inherited bone-marrow-failure syndromes (IBMFSs) include heterogeneous genetic disorders characterized by bone-marrow failure, congenital anomalies, and an increased risk of malignancy. Many lines of evidence have suggested that p53 activation might be central to the pathogenesis of IBMFSs, including Diamond-Blackfan anemia (DBA) and dyskeratosis congenita (DC). However, the exact role of p53 activation in each clinical feature remains unknown. Read More

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September 2018
13 Reads
10.930 Impact Factor

[Li-Fraumeni syndrome in a patient with multiple anaplastic oligodendrogliomas of the brain (a case report and literature review)].

Zh Vopr Neirokhir Im N N Burdenko 2018;82(4):87-96

Neurological Center of Latium, Rome, Italy; Department of Biomedicine, University of Rome Tor Vergata and NCL-Institute of Neurological Sciences, Rome, Italy.

Li-Fraumeni syndrome (LFS) is a clinically and genetically heterogeneous hereditary syndrome with predominantly oncological manifestations, which is associated with mutations in the TP53, MDM2, and CHEK2 genes. The most common variant is a TP53 mutation.

Objective: To analyze the literature and present a clinical case of a patient with Li-Fraumeni syndrome and multiple anaplastic oligodendrogliomas of the brain. Read More

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January 2018
2 Reads

Lay Perspectives on Receiving Different Types of Genomic Secondary Findings: a Qualitative Vignette Study.

J Genet Couns 2018 Aug 15. Epub 2018 Aug 15.

Department of Social Research, University of Helsinki, Unioninkatu 37, P.O. Box 54, 00014, Helsinki, Finland.

Genome-wide sequencing may generate secondary findings (SFs). It is recommended that validated, clinically actionable SFs are reported back to patients/research participants. To explore publics' perspectives on the best ways to do this, we performed a vignette study among Finnish adults. Read More

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August 2018
2 Reads

Whole-body magnetic resonance imaging of Li-Fraumeni syndrome patients: observations from a two rounds screening of Brazilian patients.

Cancer Imaging 2018 Aug 14;18(1):27. Epub 2018 Aug 14.

Centro de Oncologia, Hospital Sírio-Libanês, São Paulo, Brazil.

Background: Li-Fraumeni syndrome (LFS) is an autosomal dominant disease that is associated with germline TP53 mutations and it predisposes affected individuals to a high risk of developing multiple tumors. In Brazil, LFS is characterized by a different pattern of TP53 variants, with the founder TP53 p.R337H mutation being predominant. Read More

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August 2018
1 Read

Adrenocortical carcinoma (ACC): When and why should we consider germline testing?

Presse Med 2018 Jul - Aug;47(7-8 Pt 2):e119-e125. Epub 2018 Aug 10.

University of Michigan, Michigan Medicine, Department of Internal Medicine, Metabolism, Endocrinology and Diabetes, 500 S State St, Ann Arbor, 48109, MI, USA. Electronic address:

Adrenocortical carcinoma (ACC), particularly when occurring during childhood, has been a traditional component of the tumor spectrum of Li-Fraumeni syndrome. Recent research has defined a significant risk increase of ACC with other familial cancer syndromes, such as Lynch syndrome and multiple endocrine neoplasia. ACC patients can serve as index patients for a new family diagnosis of a hereditary syndrome, allowing for further family cascade genetic testing, impacting the care and surveillance for patients and at risk family members. Read More

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September 2018
8 Reads

Additional germline findings from a tumor profiling program.

BMC Med Genomics 2018 Aug 9;11(1):65. Epub 2018 Aug 9.

Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, 610 University Ave, Toronto, ON, M5G 2M9, Canada.

Background: Matched tumor-normal sequencing, applied in precision cancer medicine, can identify unidentified germline Medically Actionable Variants (gMAVS) in cancer predisposition genes. We report patient preferences for the return of additional germline results, and describe various gMAV scenarios delivered through a clinical genetics service.

Methods: Tumor profiling was offered to 1960 advanced cancer patients, of which 1556 underwent tumor-normal sequencing with multigene hotspot panels containing 20 cancer predisposition genes. Read More

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August 2018
10 Reads

Breast cancer patients suggestive of Li-Fraumeni syndrome: mutational spectrum, candidate genes, and unexplained heredity.

Breast Cancer Res 2018 Aug 7;20(1):87. Epub 2018 Aug 7.

Department of Human Genetics, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.

Background: Breast cancer is the most prevalent tumor entity in Li-Fraumeni syndrome. Up to 80% of individuals with a Li-Fraumeni-like phenotype do not harbor detectable causative germline TP53 variants. Yet, no systematic panel analyses for a wide range of cancer predisposition genes have been conducted on cohorts of women with breast cancer fulfilling Li-Fraumeni(-like) clinical diagnostic criteria. Read More

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August 2018
1 Read

Dual diagnoses in 152 patients with Turner syndrome: Knowledge of the second condition may lead to modification of treatment and/or surveillance.

Am J Med Genet A 2018 Nov 6;176(11):2435-2445. Epub 2018 Aug 6.

Genetics Unit, MassGeneral Hospital for Children, Boston, Massachusetts.

Turner syndrome is a sex chromosome abnormality in which a female has a single X chromosome or structurally deficient second sex chromosome. The phenotypic spectrum is broad, and atypical features prompt discussion of whether the known features of Turner syndrome should be further expanded. With the advent of clinical whole exome sequencing, there has been increased realization that some patients with genetic disorders carry a second genetic disorder, leading us to hypothesize that a "dual diagnosis" may be more common than suspected for Turner syndrome. Read More

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November 2018
9 Reads

Imaging of cancer predisposition syndromes.

Pediatr Radiol 2018 08 4;48(9):1364-1375. Epub 2018 Aug 4.

Department of Diagnostic Imaging, The Hospital for Sick Children, Department of Medical Imaging, University of Toronto, 555 University Ave., Toronto, ON, M5G 1X8, Canada.

Pediatric cancer predisposition syndromes comprise a group of diseases characterized by specific tumors or a concomitance of tumors in infants, children and adolescents, suggesting a genetic cancer susceptibility condition. Most but not all have germline pathogenic variants on genetic testing. For some children with cancer predisposition syndromes, this diagnosis is based on their own or a family history of related neoplasms, or associated clinical manifestations. Read More

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Identification and characterization of TP53 gene Allele Dropout in Li-Fraumeni syndrome and Oral cancer cohorts.

Sci Rep 2018 Aug 3;8(1):11705. Epub 2018 Aug 3.

Sarin Lab, Advanced Centre for Treatment Research and Education in Cancer-Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra, India.

Allele Drop out (ADO) arising from non-amplification of one allele may produce false negative result and impact clinical management. In cancer, germline and somatic genetic analysis is being increasingly used but the prevalence, nature and implications of ADO has not been studied in any cohort. In a cohort of 290 Li Fraumeni/Li Fraumeni Like Syndrome cases undergoing TP53 genetic testing, of the 69 pathogenic mutations identified so far, 5 were initially missed and 4 were misgenotyped as homozygous mutation due to germline ADO. Read More

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August 2018
5.080 Impact Factor

Contribution of genotoxic anticancer treatments to the development of multiple primary tumours in the context of germline TP53 mutations.

Eur J Cancer 2018 Sep 30;101:254-262. Epub 2018 Jul 30.

Normandie Univ, UNIROUEN, Inserm U1245, Rouen University Hospital, Department of Genetics, Normandy Centre for Genomic and Personalized Medicine, Rouen, France.

Introduction: Li-Fraumeni syndrome (LFS), due to TP53 germline mutations, is characterised by a remarkably high incidence of multiple primary cancers (MPCs), and the key role of p53 in response to DNA damage questions the contribution of anticancer treatments to MPCs development.

Materials And Methods: We first evaluated genotoxicity of X-rays and different classes of conventional chemotherapies, thanks to genotoxicity assays, based on the measurement of transcriptional response to DNA damage and performed in murine splenocytes, either exposed ex vivo or extracted from exposed mice. We then exposed a total of 208 Trp53Δ/Δ, wt/Δ or wt/wt mice to clinical doses of X-rays or genotoxic or non-genotoxic chemotherapies. Read More

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September 2018
4 Reads
5.420 Impact Factor

Mouse Homolog of the Human R337H Mutation Reveals Its Role in Tumorigenesis.

Cancer Res 2018 Sep 24;78(18):5375-5383. Epub 2018 Jul 24.

Cardiovascular Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland.

Inheritance of germline mutations in the tumor suppressor gene causes Li-Fraumeni syndrome (LFS), a cancer predisposition disorder. The arginine to histidine substitution at amino acid position 337 of p53 (R337H) is a founder mutation highly prevalent in southern and southeastern Brazil and is considered an LFS mutation. Although this mutation is of significant clinical interest, its role in tumorigenesis using animal models has not been described. Read More

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September 2018
19 Reads
9.330 Impact Factor

Parent-child communication surrounding genetic testing for Li-Fraumeni syndrome: Living under the cloud of cancer.

Pediatr Blood Cancer 2018 Nov 15;65(11):e27350. Epub 2018 Jul 15.

Division of Cancer Predisposition, St. Jude Children's Research Hospital, Memphis, Tennessee.

Background: Advances in the application of genetic technologies reveal a growing number of heritable disorders associated with an increased risk to develop cancer during childhood. As genetic testing is increasingly employed in the clinical setting, it is essential to understand whether parents communicate with their children about test results and to elucidate the factors that influence the content and outcomes of these conversations.

Methods: Semistructured interviews were conducted with 14 parents whose children tested positive for Li-Fraumeni syndrome (LFS). Read More

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November 2018
5 Reads

A Systematic Review of How Young People Live with Inherited Disease: What Can We Learn for Li-Fraumeni Syndrome?

J Adolesc Young Adult Oncol 2018 Oct 13;7(5):525-545. Epub 2018 Jul 13.

1 Familial Cancer Centre, Peter MacCallum Cancer Centre , Melbourne, Australia .

Purpose: Li-Fraumeni syndrome (LFS), a multiorgan cancer predisposition caused by germline TP53 mutations, confers significant cancer risks for young people (15-39 years). Yet evidence of how individuals experience this condition and the psychosocial implications are lacking. Therefore, this systematic review assessed the psychosocial implications of living with, or at risk of, an autosomal dominant condition as a young person, to draw evidence that may be analogous for young people with LFS. Read More

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October 2018
7 Reads

Radiation-induced angiosarcoma of the breast in a Li-Fraumeni patient.

Cir Esp 2018 Jul 9. Epub 2018 Jul 9.

Unidad de Mama, Servicio de Oncología Médica, Complejo Hospitalario Universitario de A Coruña, A Coruña, España.

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July 2018
2 Reads

Surgical Treatment of Intramedullary Spinal Metastasis in Medulloblastoma: Case Report and Review of the Literature.

World Neurosurg 2018 Oct 7;118:42-46. Epub 2018 Jul 7.

Department of Neurosurgery, Nicklaus Children's Hospital, Miami, Florida, USA; Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, Florida, USA.

Background: Medulloblastomas are common childhood central nervous system tumors that are prone to leptomeningeal spread. Intramedullary dissemination is rare with very few case reports existing in the available literature.

Case Description: The authors here present a case of a 14-year-old boy with Li-Fraumeni syndrome and medulloblastoma who underwent surgical resection of spinal intramedullary spread. Read More

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October 2018
2 Reads

65 YEARS OF THE DOUBLE HELIX: Endocrine tumour syndromes in children and adolescents.

Endocr Relat Cancer 2018 Aug;25(8):T221-T244

Department of Human GeneticsResearch Institute of the McGill University Health Centre, and Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Canada

As medicine is poised to be transformed by incorporating genetic data in its daily practice, it is essential that clinicians familiarise themselves with the information that is now available from more than 50 years of genetic discoveries that continue unabated and increase by the day. Endocrinology has always stood at the forefront of what is called today 'precision medicine': genetic disorders of the pituitary and the adrenal glands were among the first to be molecularly elucidated in the 1980s. The discovery of two endocrine-related genes, and , both identified in the late 1980s, contributed greatly in the understanding of cancer and its progression. Read More

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August 2018
10 Reads

Modeling Osteosarcoma Using Li-Fraumeni Syndrome Patient-derived Induced Pluripotent Stem Cells.

J Vis Exp 2018 06 13(136). Epub 2018 Jun 13.

Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston; Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center UTHealth; Center for Stem Cell and Regenerative Medicine, The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, The University of Texas Health Science Center at Houston; Center for Precision Health, School of Biomedical Informatics and School of Public Health, The University of Texas Health Science Center at Houston;

Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer disorder. Patients with LFS are predisposed to a various type of tumors, including osteosarcoma--one of the most frequent primary non-hematologic malignancies in the childhood and adolescence. Therefore, LFS provides an ideal model to study this malignancy. Read More

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June 2018
8 Reads

Association Between the Oligomeric Status of p53 and Clinical Outcomes in Li-Fraumeni Syndrome.

J Natl Cancer Inst 2018 Jun 27. Epub 2018 Jun 27.

Department of Medical Biophysics.

Li-Fraumeni syndrome (LFS) is a rare hereditary cancer disorder with highly variable clinical outcomes that results from germline mutations in the TP53 gene. Here we report that the quaternary structure of p53 is an important factor affecting cellular functions and the clinical outcomes of LFS patients (n = 87). Specifically, carriers of monomeric p53 mutants (n = 56) exhibited complete penetrance, with a 2. Read More

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Surveillance Screening in Li-Fraumeni Syndrome: Raising Awareness of False Positives.

Cureus 2018 Apr 24;10(4):e2527. Epub 2018 Apr 24.

Pediatrics, NYU Langone Medical Center, New York, NEW YORK, USA.

Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome inherited in an autosomal dominant fashion that involves a germline mutation of tumor protein 53 (TP53). With the advent of more accessible and accurate genetic testing methods, along with more widespread knowledge of LFS, asymptomatic carriers can now be more easily identified. No general surveillance protocols were previously recommended other than routine physical exams and breast and colon cancer screening at younger ages, primarily due to questions involving efficacy, cost, and clinical benefits. Read More

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What Should a Gynecologist Know about Li-Fraumeni Syndrome? Lessons from a Patient Undergoing Hysterectomy for Benign Indications.

Gynecol Obstet Invest 2018 26;83(4):410-414. Epub 2018 Jun 26.

Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia, USA.

Li-Fraumeni syndrome (LFS) is a rare highly penetrant cancer syndrome characterized by mutation in the TP53 tumor suppressor gene. Recent data suggest that this germline mutation is more frequent than once thought. While LFS has not been associated previously with pelvic serous carcinoma, gynecologic malignancies have been reported in this patient population. Read More

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October 2018
15 Reads

Li-Fraumeni Syndrome-related Malignancies Involving the Genitourinary Tract: Review of a Single-institution Experience.

Urology 2018 Sep 21;119:55-61. Epub 2018 Jun 21.

Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Weill Cornell Medical College, New York, NY.

Objective: To report a case of pelvic angiosarcoma in a 27-year-old man with Li-Fraumeni Syndrome (LFS) and evaluate the presentation and timeline of genitourinary (GU) tract involvement in LFS patients.

Methods: We retrospectively identified 39 LFS patients treated at our institution between 2000 and 2014; 7 (18%) had experienced a GU malignancy or an LFS-related malignancy involving the GU tract. Clinical characteristics, including dates of onset of first GU tract malignancies; pathologic findings; multimodal management; and familial history of LFS were reviewed. Read More

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September 2018
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The Influence of Adolescence on Parents' Perspectives of Testing and Discussing Inherited Cancer Predisposition.

J Genet Couns 2018 Jun 16. Epub 2018 Jun 16.

Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Li-Fraumeni syndrome (LFS) is a highly penetrant cancer predisposition syndrome that may present with a first cancer before or during adolescence/young adulthood. Families offered LFS genetic testing for their children can inform our understanding of how the unique developmental context of adolescence influences parental perspectives about genetic testing and discussions of cancer risk. In this study, semi-structured interviews were conducted with 46 parents of children at risk for LFS to capture those perspectives. Read More

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June 2018
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