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Jpn J Clin Oncol 2020 Jun 24. Epub 2020 Jun 24.

Department of Clinical Oncology, Akita University, Akita, Japan.

Germline mutations of TP53 are responsible for Li-Fraumeni syndrome in its 60-80%. We found a novel germline mutation, TP53: c.997del:p. Read More

J Pediatr Hematol Oncol 2020 Jul;42(5):e265-e270

Department of Pediatric and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University Medical Center Freiburg, University of Freiburg.

Background: The occurrence of prior, concurrent and subsequent neoplasms (SN) represents a serious problem in children and adolescents with soft tissue sarcomas. Pathogenic germline variants contribute to the diagnosis of multiple neoplasms in sarcoma survivors.

Materials And Methods: The records of 748 children and adolescents, diagnosed with soft tissue sarcomas and registered in trials/registries by the cooperative soft tissue sarcoma (Cooperative Weichteilsarkom Studie) group, were reviewed for the occurrence of SNs. Read More

J Med Genet 2020 Jun 22. Epub 2020 Jun 22.

Genetic Medicine, Central Manchester University Hospitals NHS FoundationTrust, Manchester, UK.

Constitutional pathogenic variants in are associated with Li-Fraumeni syndrome or the more recently described heritable related cancer syndrome and are associated with increased lifetime risks of a wide spectrum of cancers. Due to the broad tumour spectrum, surveillance for this patient group has been limited. To date, the only recommendation in the UK has been for annual breast MRI in women; however, more recently, a more intensive surveillance protocol including whole-body MRI (WB-MRI) has been recommended by International Expert Groups. Read More

Cancer 2020 Jun 18. Epub 2020 Jun 18.

Department of Gynecology and Obstetrics, University Hospital Heidelberg, Heidelberg, Germany.

Background: Li-Fraumeni syndrome (LFS) is a high-risk cancer predisposition syndrome caused by pathogenic germline variants of TP53. Cancer surveillance has noted a significant survival advantage in individuals with LFS; however, little is known about the feasibility, acceptance, and psychosocial effects of such a program.

Methods: Pathogenic TP53 germline variant carriers completed a 7-part questionnaire evaluating sociodemographics, cancer history, surveillance participation, reasons for nonadherence, worries, and distress adapted from the Cancer Worry Scale. Read More

J Pediatr Hematol Oncol 2020 Jun 16. Epub 2020 Jun 16.

Department of Pediatrics, Mie University Graduate School of Medicine, Mie, Japan.

Li-Fraumeni syndrome (LFS) is a rare inherited disease characterized by a high and early-onset cancer risk. A cancer surveillance program is important to reduce cancer-related morbidity and mortality in individuals with LFS. We report 2 pediatric cases with LFS-related malignancy in a family. Read More

PLoS One 2020 9;15(6):e0234262. Epub 2020 Jun 9.

Department of Hematology & Oncology, Key Laboratory of Pediatric Hematology and Oncology Ministry of Health, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

p53 is one of the most extensively studied proteins in cancer research. Mutations in p53 generally abolish normal p53 function, and some mutants can gain new oncogenic functions. However, the mechanisms underlying p53 mutation-driven cancer remains to be elucidated. Read More

Best Pract Res Clin Endocrinol Metab 2020 May 23:101428. Epub 2020 May 23.

Section on Endocrinology and Genetics & Inter-Institute Endocrinology Fellowship Program, Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health (NIH), Bethesda, MD, 20892, USA. Electronic address:

Advances in genomics over the past two decades have allowed for elucidation of the genetic alterations leading to the development of adrenocortical tumors and/or hyperplasias. These molecular changes were initially discovered through the study of rare familial tumor syndromes such as McCune-Albright Syndrome, Carney complex, Li-Fraumeni syndrome, and Beckwith-Wiedemann syndrome, with the identification of alterations in genes and molecular pathways that subsequently led to the discovery of aberrations in these or related genes and pathways in sporadic tumors. Genetic alterations in GNAS, PRKAR1A, PRKACA, PRKACB, PDE11A, and PDE8B, that lead to aberrant cyclic adenosine monophosphate-protein (cAMP) kinase A signaling, were found to play a major role in the development of benign cortisol-producing adrenocortical tumors and/or hyperplasias, whereas genetic defects in KCNJ5, ATP1A1, ATP2B3, CACNA1D, CACNA1H, and CLCN2 were implicated in the development of benign aldosterone-producing tumors and/or hyperplasias through modification of intracellular calcium signaling. Read More

Ann Surg Oncol 2020 Jun 5. Epub 2020 Jun 5.

Department of Surgery, Mayo Clinic, Rochester, MN, USA.

Background: A paucity of data exists regarding inherited mutations associated with phyllodes tumors (PT); however, some are reported (TP53, BRCA1, and RB1). A PT diagnosis does not meet NCCN criteria for testing, including within Li-Fraumeni Syndrome (TP53). We sought to determine the prevalence of mutations associated with PT. Read More

Hum Mutat 2020 Jun 2. Epub 2020 Jun 2.

Genetics and Computational Division, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.

Early onset breast cancer is the most common malignancy in women with Li-Fraumeni syndrome, caused by germline TP53 pathogenic variants. It has repeatedly been suggested that breast tumors from TP53 carriers are more likely to be HER2+ than those of noncarriers, but this information has not been incorporated into variant interpretation models for TP53. Breast tumor pathology is already being used quantitatively for assessing pathogenicity of germline variants in other genes, and it has been suggested that this type of evidence can be incorporated into current American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines for germline variant classification. Read More

Eur J Hum Genet 2020 May 26. Epub 2020 May 26.

Manchester Centre for Genomic Medicine, Division of Evolution and Genomic Sciences, University of Manchester, MAHSC, St Mary's Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester, UK.

Fifty years after the recognition of the Li-Fraumeni syndrome (LFS), our perception of cancers related to germline alterations of TP53 has drastically changed: (i) germline TP53 alterations are often identified among children with cancers, in particular soft-tissue sarcomas, adrenocortical carcinomas, central nervous system tumours, or among adult females with early breast cancers, without familial history. This justifies the expansion of the LFS concept to a wider cancer predisposition syndrome designated heritable TP53-related cancer (hTP53rc) syndrome; (ii) the interpretation of germline TP53 variants remains challenging and should integrate epidemiological, phenotypical, bioinformatics prediction, and functional data; (iii) the penetrance of germline disease-causing TP53 variants is variable, depending both on the type of variant (dominant-negative variants being associated with a higher cancer risk) and on modifying factors; (iv) whole-body MRI (WBMRI) allows early detection of tumours in variant carriers and (v) in cancer patients with germline disease-causing TP53 variants, radiotherapy, and conventional genotoxic chemotherapy contribute to the development of subsequent primary tumours. It is critical to perform TP53 testing before the initiation of treatment in order to avoid in carriers, if possible, radiotherapy and genotoxic chemotherapies. Read More

J Psychosoc Oncol 2020 May 25:1-20. Epub 2020 May 25.

Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

This study explored the genetic testing experiences of adolescents and young adults (AYAs; aged 15-39 years) with, or at 50% risk of, an early onset cancer predisposition syndrome: Li-Fraumeni syndrome (LFS). We used interpretive description and conducted semi-structured interviews with 30 AYAs (mean age 25.5 years): 26 with LFS and four at 50% risk. Read More

Hum Mol Genet 2020 May 15. Epub 2020 May 15.

Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105.

Wilms tumor (WT), the most common childhood kidney cancer, develops in association with an underlying germline predisposition in up to 15% of cases. Germline alterations affecting the WT1 gene and epigenetic alterations affecting the 11p15 locus are associated with a selective increase in WT risk. Nevertheless, WT also occurs in the context of more pleiotropic cancer predispositions, such as DICER1, Li-Fraumeni, and Bloom syndrome, as well as Fanconi anemia. Read More

Fam Cancer 2020 Apr 30. Epub 2020 Apr 30.

Department of Dermatology, Netherlands Cancer Institute, Plesmanlaan 12, 1066, CX, Amsterdam, The Netherlands.

Li-Fraumeni syndrome (LFS) is an inherited cancer syndrome, characterized by an early onset of various types of cancers. LFS is associated with a germline mutation in the TP53 gene. The risk of developing skin cancer in patients with LFS is unknown. Read More

J Immunother Cancer 2020 Apr;8(1)

Department of Hematology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China

Background: Li-Fraumeni syndrome (LFS) is characterized as an autosomal dominant cancer predisposition disorder caused by germline gene mutations. Both primary and therapy-related hematopoietic malignancies with LFS are associated with dismal outcomes with standard therapies and even allogenic stem cell transplantation (SCT).

Case Presentation: We reported a relapsed/refractory acute B-cell lymphoblastic lymphoma (B-LBL) patient in the context of LFS. Read More

Radiol Clin North Am 2020 May;58(3):619-638

Division of Thoracic Imaging, Department of Radiology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA. Electronic address:

Genetic syndromes are an infrequently encountered but challenging group of conditions for both pediatric and adult radiologists given the multitude of possible findings and important complications associated with these syndromes. This article reviews characteristic syndromic imaging features, as well as discussing important complications and screening recommendations for a selected group of clinically relevant genetic syndromes affecting both pediatric and adult populations. Read More

Breast Cancer Res Treat 2020 May 3;181(1):181-188. Epub 2020 Apr 3.

Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

Purpose: Women with Li-Fraumeni syndrome (LFS), a cancer predisposition syndrome caused by germline mutations in TP53, have an over 50% risk of developing breast cancer by age 70. Patients with LFS are at risk for radiation-induced malignancies; however, only small case series have prior investigated radiation risks in the treatment of breast cancer. We therefore aimed to investigate the risk of malignancy in breast cancer patients with LFS following adjuvant radiotherapy. Read More

Case Rep Oncol 2020 Jan-Apr;13(1):130-138. Epub 2020 Feb 13.

Medical Oncology Department, Badalona Applied Research Group in Oncology (B-ARGO Group), Catalan Institute of Oncology, Badalona, Spain.

Germline mutations in TP53, a tumor suppressor gene, are involved in the development of Li-Fraumeni syndrome, a rare disorder that predisposes carriers to multiple tumors. TP53 mutations have been associated with resistance to treatment and poor prognosis. A young female with the pathogenic germline TP53 mutation c. Read More

BMC Cancer 2020 Mar 30;20(1):256. Epub 2020 Mar 30.

Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Building 10, Room 4-5952, Bethesda, MD, 20892, USA.

Background: Li-Fraumeni syndrome is a cancer predisposition syndrome caused by germline TP53 tumor suppressor gene mutations, with no previous association with pancreatic neuroendocrine tumors (PNETs). Here we present the first case of PNET associated with Li-Fraumeni syndrome.

Case Presentation: This is a 43-year-old female who underwent laparoscopic distal pancreatectomy at age 39 for a well-differentiated grade 2 cystic PNET. Read More

Rev Bras Ginecol Obstet 2020 Feb 30;42(2):114-119. Epub 2020 Mar 30.

Universidade do Oeste Paulista, Presidente Prudente, SP, Brazil.

Several factors trigger the development of genetic mutations that are responsible for causing a neoplasm. Medulloblastoma is a malignant and invasive cerebellar neoplasm, that affects children and young adults. Mucinous carcinoma is a special type of breast cancer. Read More

Fam Cancer 2020 Jul;19(3):259-268

Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.

Li-Fraumeni Syndrome (LFS) is characterized by risk of multiple primary malignancies in diverse sites, pediatric onset, near complete penetrance by age 70 years, limited options for prevention, and substantial uncertainty regarding disease manifestation and prognosis. Forty-five families, including 117 individuals aged 13-81 years, enrolled in the US National Cancer Institute's Li-Fraumeni Syndrome Study completed 66 interviews regarding their LFS experiences. An interdisciplinary team used modified grounded theory to examine family distress regarding expectations of loss and change due to likely cancer diagnoses, and the consequences of this likelihood across physical, social, and emotional domains. Read More

Am Soc Clin Oncol Educ Book 2020 Mar;40:1-12

Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.

Secondary sarcomas are a subset of sarcomas that occur in patients with prior cancer diagnoses and are associated with environmental or genetic factors. Although secondary sarcomas are rare in general, there are predisposing factors that can substantially increase this risk in certain populations. Herein, we review the environmental factors with the strongest association of sarcoma risk, including chemical exposure, certain viruses, cytotoxic and immunosuppressive agents, chronic edema, and radiation exposure. Read More

Ann Pathol 2020 Apr 17;40(2):168-179. Epub 2020 Mar 17.

Département de pathologie cellulaire et tissulaire, CHU d'Angers, 4, rue Larrey, 49100 Angers, France; CRCINA, université de Nantes, université d'Angers, 49100 Angers, France. Electronic address:

Some tumors of the central and peripheral nervous system may be associated with a cancer predisposition syndrome, either hereditary or occurring de novo. Such a syndrome is usually associated with multiple tumors occurring early in life. Patients with neurofibromatosis type 1 present with multiple neurofibromas, especially of the plexiform type (which may transform into malignant peripheral nerve sheath tumor), and pilocytic astrocytomas of the optic pathways. Read More

JAMA Oncol 2020 Mar 19. Epub 2020 Mar 19.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Importance: Osteosarcoma, the most common malignant bone tumor in children and adolescents, occurs in a high number of cancer predisposition syndromes that are defined by highly penetrant germline mutations. The germline genetic susceptibility to osteosarcoma outside of familial cancer syndromes remains unclear.

Objective: To investigate the germline genetic architecture of 1244 patients with osteosarcoma. Read More

J Cutan Pathol 2020 Mar 18. Epub 2020 Mar 18.

Department of Pathology, Stanford University School of Medicine, Stanford, California.

Pleomorphic fibromas are rare benign cutaneous neoplasms associated with deletion/loss of chromosomes 13q and 17p, where RB1 and TP53 are located, respectively. Herein, we report five cases of pleomorphic fibroma arising in patients with germline TP53 mutations, suggesting a potential link with Li-Fraumeni syndrome. All three patients were female and young (mean age 27) with a strong personal and/or family oncologic history and confirmed pathogenic germline TP53 mutations. Read More

J Thorac Oncol 2020 Jul 14;15(7):1232-1239. Epub 2020 Mar 14.

Thoracic Oncology Group, Cancer Medicine Department, Gustave Roussy, Villejuif, France; INSERM, Gustave Roussy Cancer Campus, Université Paris Saclay, Saint-Aubin, France.

Introduction: Actionable somatic molecular alterations are found in 15% to 20% of NSCLC in Europe. NSCLC is a tumor observed in patients with germline TP53 variants causing Li-Fraumeni syndrome (LFS), but its somatic molecular profile is unknown.

Methods: Retrospective study of clinical and molecular profiles of patients with NSCLC and germline TP53 variants. Read More

Acta Neuropathol 2020 May 10;139(5):953-957. Epub 2020 Mar 10.

Department of Pathology, University of California, San Francisco, CA, USA.

Cancer Epidemiol Biomarkers Prev 2020 May 10;29(5):927-935. Epub 2020 Mar 10.

City of Hope National Medical Center, Duarte, California.

Background: The success of multisite collaborative research relies on effective data collection, harmonization, and aggregation strategies. Data Coordination Centers (DCC) serve to facilitate the implementation of these strategies. The utility of a DCC can be particularly relevant for research on rare diseases where collaboration from multiple sites to amass large aggregate datasets is essential. Read More

Cureus 2020 Jan 7;12(1):e6590. Epub 2020 Jan 7.

Radiology, University of Texas Medical Branch, Galveston, USA.

Breast cancer is the most commonly diagnosed cancer and the second leading cause of cancer death in women. Early detection, accurate diagnosis and proper treatment are important prognostic factors due to the wide variety of breast cancer subtypes. This becomes of particular importance with rare breast tumors, which are difficult to diagnose due to their varying presentations. Read More

Radiographics 2020 Mar-Apr;40(2):306-325. Epub 2020 Feb 7.

From the Departments of Radiology (S.H.C., R.M., M.M.J., M.K.P.), Clinical Genetics (W.C.), and Obstetrics and Gynecology (J.G.C.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, Calif; Hoag Hospital, Newport Harbor Radiology Associates, Newport Beach, Calif (N.W.); and Department of Radiology, Olive View-UCLA Medical Center, Sylmar, Calif (A.R.R.).

In addition to the well-characterized and hereditary breast and ovarian cancer syndromes, many other syndromes that are associated with genetic mutations predispose individuals to an increased risk of breast and gynecologic malignancies. Many mutated genes encode for tumor-suppressor products and are inherited in an autosomal dominant manner. Mutations markedly increase an individual's lifetime risk of cancers in different organ systems, depending on the associated syndrome. Read More

Oncogene 2020 Mar 30;39(13):2692-2706. Epub 2020 Jan 30.

Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.

Alterations of the retinoblastoma and/or the p53 signaling network are associated with specific cancers such as high-grade astrocytoma/glioblastoma, small-cell lung cancer (SCLC), choroid plexus tumors, and small-cell pancreatic neuroendocrine carcinoma (SC-PaNEC). However, the intricate functional redundancy between RB1 and the related pocket proteins RBL1/p107 and RBL2/p130 in suppressing tumorigenesis remains poorly understood. Here we performed lineage-restricted parallel inactivation of rb1 and rbl1 by multiplex CRISPR/Cas9 genome editing in the true diploid Xenopus tropicalis to gain insight into this in vivo redundancy. Read More

PLoS One 2020 24;15(1):e0227260. Epub 2020 Jan 24.

Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.

Sarcomas represent less than 1% of all solid neoplasms in adults and over 20% in children. Their etiology is unclear, but genetic susceptibility plays an important role in this scenario. Sarcoma is central in Li-Fraumeni Syndrome (LFS), a familial predisposition cancer syndrome. Read More

J Surg Case Rep 2020 Jan 13;2020(1):rjz386. Epub 2020 Jan 13.

Maxillofacial Surgery Unit, Centro Hospitalar e Universitário do Porto, Porto, Portugal.

Mesenchymal chondrosarcoma (MCS) is a rare histological variant of chondrosarcoma, with aggressive behaviour. Due to the unique nature of this disease, management strategies are not well established. Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome with a wide tumour spectrum, associated with TP53 germline mutations. Read More

Acta Neuropathol 2020 Apr 22;139(4):703-715. Epub 2020 Jan 22.

The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Canada.

Cancer predisposition syndromes are associated with an increased risk of developing primary malignancies. Here we discuss those which are associated with an increased risk of tumors of the central nervous system (CNS) and gastrointestinal (GI) tract. These can be grouped into those in which the CNS tumors predominate versus those in which the GI cancers predominate. Read More

Neuro Oncol 2020 Jun;22(6):864-874

Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.

Background: Pediatric astrocytoma constitutes a majority of malignant pediatric brain tumors. Previous studies that investigated pediatric cancer predisposition have primarily been conducted in tertiary referral centers and focused on cancer predisposition genes. In this study, we investigated the contribution of rare germline variants to risk of malignant pediatric astrocytoma on a population level. Read More

Cell Rep 2020 Jan;30(3):783-792.e5

Cardiovascular Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA. Electronic address:

The physiological effects of the many germline mutations of TP53, encoding the tumor suppressor protein p53, are poorly understood. Here we report generating a p53 R178C knockin mouse modeling the human TP53 R181C mutation, which is notable for its prevalence and prior molecular characterization. Consistent with its weak cancer penetrance in humans, homozygous p53 mice show a modest increase in tumorigenesis but, surprisingly, are lean with decreased body fat content. Read More

Pediatr Neurol 2020 03 15;104:3-12. Epub 2019 Aug 15.

Division of Pediatric Hematology and Oncology, Department of Pediatrics, Texas Children's Hospital/Baylor College of Medicine, Houston, Texas.

Central nervous system tumors are the most common solid tumors in pediatrics and represent the largest cause of childhood cancer-related mortality. Improvements have occurred in the management of these patients leading to better survival, but significant morbidity persists. With the era of next generation sequencing, considerable advances have occurred in the understanding of these tumors both biologically and clinically. Read More

Endocrinol Diabetes Metab Case Rep 2020 Jan 8;2020. Epub 2020 Jan 8.

Pediatric Oncology Branch, Rare Tumor Initiative, Center for Cancer Research, National Cancer Institute, Clinical Center.

Summary: Adrenocortical carcinoma (ACC) is an aggressive cancer that originates in the cortex of the adrenal gland and generally has a poor prognosis. ACC is rare but can be more commonly seen in those with cancer predisposition syndromes (e.g. Read More

Biochim Biophys Acta Rev Cancer 2020 01 7;1873(1):188339. Epub 2020 Jan 7.

LAQV/REQUIMTE, Laboratory of Microbiology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal. Electronic address:

Increasing emphasis has been given to prevention as a feasible approach to reduce the cancer burden. However, for its clinical success, further advances are required to identify effective chemopreventive agents. This review affords a critical and up-to-date discussion of issues related to cancer prevention, including an in-depth knowledge on BRCA1 and p53 tumor suppressor proteins as key molecular players. Read More

J Med Case Rep 2020 Jan 8;14(1). Epub 2020 Jan 8.

Hematology/Oncology Department, Fundación Valle del Lili, Cali, Carrera 98 No. 18-49, Colombia.

Background: Multiple primary malignant neoplasms are not frequent but are increasing in incidence. Some of them are associated with genetic syndromes such as von Hippel-Lindau syndrome and Li-Fraumeni syndrome. Dedifferentiated liposarcoma is one of the rarest soft tissue tumors, and clear cell renal carcinoma is the most frequent kidney cancer. Read More

J Biol Chem 2020 01;295(1):290

Hum Mutat 2020 Mar 16;41(3):537-542. Epub 2020 Jan 16.

Genetics and Computational Division, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.

The American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines for variant classification are widely used for clinical interpretation of gene test results. These guidelines may be specified to genes/syndromes of interest to improve their utility in the clinical setting. As part of these specifications, phenotype-related criteria can be detailed and weighted depending on the personal history of disease for a given variant carrier. Read More

Acta Neuropathol 2020 Apr 3;139(4):795-797. Epub 2020 Jan 3.

Prague Brain Tumor Research Group, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic.

Clin Lung Cancer 2020 Mar 28;21(2):e37-e44. Epub 2019 Nov 28.

Genomics and Molecular Biology Laboratory, CIPE, A. C. Camargo Cancer Center, São Paulo, Brazil; National Institute of Science and Technology in Oncogenomics (INCITO), São Paulo, Brazil. Electronic address:

Case Rep Oncol Med 2019 27;2019:7950782. Epub 2019 Nov 27.

HealthPartners Neuroscience Center, St Paul, MN, USA.

Radiation-induced sarcomas in the brain are extremely rare, usually occur with an average latency of 9 years, and are associated with poor outcomes. Latency periods shorter than 1 year may indicate a genetic predisposition such as Li-Fraumeni syndrome. A 34-year-old man underwent initial tumor resection and radiation therapy for a World Health Organization (WHO) Grade II Astrocytoma. Read More

J Mol Diagn 2020 Mar 24;22(3):396-404. Epub 2019 Dec 24.

Inherited Cancer Program, GeneDx, Inc., Gaithersburg, Maryland.

Heterozygous (HET) TP53 pathogenic variants (PVs) are associated with Li-Fraumeni syndrome (LFS), a dominantly inherited condition causing high risk for sarcoma, breast, and other cancers. Recent reports describe patients without features of LFS and apparently HET TP53 PVs in blood cells but not fibroblasts (FBs), suggesting the variant occurred sporadically during hematopoiesis and rose to high allele fraction through clonal expansion. To explore possible clonal hematopoiesis in patients undergoing hereditary cancer testing, FB testing was performed for patients with apparently HET or mosaic TP53 PVs identified in blood, oral rinse, or buccal specimens via next-generation sequencing panels. Read More

J Genet Couns 2019 Dec 23. Epub 2019 Dec 23.

Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre, Melbourne, Vic., Australia.

Li-Fraumeni syndrome (LFS), a rare cancer syndrome caused by pathogenic germline variants in TP53, has serious implications for adolescents and young adults (AYAs; aged 15-39 years). The early-onset and multi-organ cancer risk associated with LFS means health professionals must concurrently contend with the developmental needs of individuals who are diagnosed from a young age, and recent changes in practice due to advances in whole-body cancer surveillance. To help understand how current practice meets the developmental needs of AYAs with, or at risk of, LFS, we conducted a national online survey to explore the experiences of health professionals who care for this population in Australia and New Zealand. Read More

Case Rep Orthop 2019 13;2019:8732089. Epub 2019 Nov 13.

Department of Pediatric Orthopedics, Necker-Enfants Malades Hospital, AP-HP, University Paris Descartes, 149 Rue de Sèvres, 75014 Paris, France.

Li-Fraumeni syndrome is a rare inherited disease characterized by the early onset of multiple primary malignant tumors. Sarcomas account for more than 30% of all malignant tumors occurring at pediatric age. Furthermore, it was shown that the rates of second cancer were higher in childhood cancer survivors. Read More

Cancer Genet 2020 Jan 20;240:54-58. Epub 2019 Nov 20.

Post-Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil; Genomic Medicine Laboratory, Experimental Research Center, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil; Medical Genetics Service, HCPA, Porto Alegre, Rio Grande do Sul, Brazil; Department of Genetics, UFRGS, Porto Alegre, Rio Grande do Sul, Brazil.

Li-Fraumeni and Li-Fraumeni-like (LFS/LFL) Syndrome are cancer predisposition syndromes caused by germline pathogenic variants in TP53 and are associated with an increased risk of multiple early-onset cancers. In Southern and Southeastern Brazil, a germline founder variant with partial penetrance located in the oligomerization domain of TP53, c.1010G>A p. Read More

Obstet Gynecol 2019 12;134(6):e143-e149

A hereditary cancer syndrome is a genetic predisposition to certain types of cancer, often with onset at an early age, caused by inherited pathogenic variants in one or more genes. Most hereditary cancer syndromes exhibit autosomal dominant inheritance. The most common hereditary cancer syndromes related to women's cancer include hereditary breast and ovarian cancer syndrome, Lynch syndrome, Li-Fraumeni syndrome, Cowden syndrome, Peutz-Jeghers syndrome, and hereditary diffuse gastric cancer. Read More

Obstet Gynecol 2019 12;134(6):1366-1367

A hereditary cancer syndrome is a genetic predisposition to certain types of cancer, often with onset at an early age, caused by inherited pathogenic variants in one or more genes. Most hereditary cancer syndromes exhibit autosomal dominant inheritance. The most common hereditary cancer syndromes related to women's cancer include hereditary breast and ovarian cancer syndrome, Lynch syndrome, Li-Fraumeni syndrome, Cowden syndrome, Peutz-Jeghers syndrome, and hereditary diffuse gastric cancer. Read More