Search Our Scientific Publications & Authors

PLoS Genet 2022 Jun 21;18(6):e1010260. Epub 2022 Jun 21.

Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), Madrid, Spain.

The shelterin protein POT1 has been found mutated in many different familial and sporadic cancers, however, no mouse models to understand the pathobiology of these mutations have been developed so far. To address the molecular mechanisms underlying the tumorigenic effects of POT1 mutant proteins in humans, we have generated a mouse model for the human POT1R117C mutation found in Li-Fraumeni-Like families with cases of cardiac angiosarcoma by introducing this mutation in the Pot1a endogenous locus, knock-in for Pot1aR117C. We find here that both mouse embryonic fibroblasts (MEFs) and tissues from Pot1a+/ki mice show longer telomeres than wild-type controls. Read More

Am J Case Rep 2022 Jun 14;23:e936455. Epub 2022 Jun 14.

Department of Clinical Genetics, National Hospital Organization Nagoya Medical Center, Nagoya, Aichi, Japan.

BACKGROUND Clonal hematopoiesis is the production of a specific single clonal type of cell in the blood and is often found in cancer genomic profiling tests. When the clone carries a pathogenic variant, it may be important to differentiate between somatic or germline origin. The variant in the blood that has a lower minor allele frequency could reflect heterozygous germline origin, somatic mosaicism, and clonal hematopoiesis. Read More

Cureus 2022 Apr 29;14(4):e24602. Epub 2022 Apr 29.

Pathology and Laboratory Medicine, London Regional Cancer Program, London, CAN.

Thymomas are among the most common cancers of the anterior mediastinum. They rarely occur in patients with Li-Fraumeni syndrome (LFS), a hereditary syndrome that predisposes individuals to cancer and is characterized by mutations in the tumor suppressor encoding gene . Here we describe a case of primary thymoma in a woman diagnosed with LFS. Read More

Cancer Epidemiol Biomarkers Prev 2022 Jun 2. Epub 2022 Jun 2.

Latin American School of Oncology, Sierra Madre, CA, United States.

Background: Though germline TP53 pathogenic/likely pathogenic variants (PV) are associated with Li-Fraumeni syndrome, many detected by multigene panels represent aberrant clonal expansion (ACE), most due to clonal hematopoiesis (CH). Discerning ACE/CH from germline variants and post-zygotic mosaicism (PZM) is critically needed for risk assessment and management.

Methods: Participants in the Li Fraumeni & TP53 Understanding & Progress (LiFT UP) study with a TP53 PV were eligible. Read More

Pediatr Blood Cancer 2022 Jun 2:e29766. Epub 2022 Jun 2.

Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India.

Biomolecules 2022 Apr 27;12(5). Epub 2022 Apr 27.

Laboratory of Molecular Genetics and Cytogenetics, Institute of Biological Sciences I (ICB I), Federal University of Goiás, Goiânia 74690900, Brazil.

gene mutation is the most common genetic alteration in human malignant tumors and is mainly responsible for Li-Fraumeni syndrome. Among the several cancers related to this syndrome, breast cancer (BC) is the most common. The p. Read More

Endokrynol Pol 2022 May 20. Epub 2022 May 20.

Pediatric Oncology Department, São João University and Hospital Centre, Porto, Portugal.

Not required for clinical vignette. Read More

Clin Nucl Med 2022 May 11. Epub 2022 May 11.

From the Department of Nuclear Medicine, Beijing Friendship Hospital of Capital Medical University, Beijing, China.

Abstract: A 17-month-old girl underwent FDG PET/CT to evaluate a right adrenal lesion, which showed abnormal 18F-FDG avidity. In addition, an unexpected lesion with mild 18F-FDG uptake was noted in the right anterior thoracic wall. Pathology demonstrated adrenocortical carcinoma in the right adrenal and rhabdosarcoma in both the left forearm and right anterior thoracic wall. Read More

Zhonghua Bing Li Xue Za Zhi 2022 May;51(5):458-460

Department of Pathology, the Affiliated Hospital of Qingdao University, Qingdao 266003, China.

Klin Onkol 2022 ;35(2):119-127

Background: Ionizing radiation DNA damage is the main mechanism of radiotherapy (RT) action and the outcome of treatment and healthy tissue toxicity is influenced by a number of external and internal factors, including mutations in DNA damage recognition and repair. Disorders of DNA repair may result in increased sensitivity to cancer treatment.

Purpose: The mechanism of DNA repair and an overview of genetic syndromes with mutations in genes involved in DNA repair clarify the accelerated carcinogenesis and increased radiosensitivity in RT cancers. Read More

Am J Surg Pathol 2022 Apr 22. Epub 2022 Apr 22.

Swabian Childrens' Cancer Center, University Hospital Augsburg and EU-RHAB Registry.

Atypical teratoid/rhabdoid tumor (AT/RT) is a malignant central nervous system tumor predominantly affecting infants. Mutations ofSMARCB1or (rarely)SMARCA4causing loss of nuclear SMARCB1 or SMARCA4 protein expression are characteristic features, but further recurrent genetic alterations are lacking. Most AT/RTs occur de novo, but secondary AT/RTs arising from other central nervous system tumors have been reported. Read More

Cardiooncology 2022 Apr 18;8(1). Epub 2022 Apr 18.

Lehigh Valley Heart Institute, Lehigh Valley Health Network, Allentown, PA, USA.

Acute pericarditis is caused by the inflammation of the pericardium which can result in an effusion around the heart. Proton beam therapy causing radiation-induced pericarditis is not a well-known cause of pericarditis. We present a case of a patient with Li-Fraumeni Syndrome who developed acute onset pericarditis, presumed to be secondary to proton beam therapy. Read More

Onco Targets Ther 2022 8;15:381-405. Epub 2022 Apr 8.

Department of Gynecologic Oncology, Medical University Pleven, Pleven, Bulgaria.

Hereditary cancer syndromes are defined as syndromes, where the genetics of cancer are the result of low penetrant polymorphisms or of a single gene disorder inherited in a mendelian fashion. During the last decade, compelling evidence has accumulated that approximately 5-10% of all cancers could be attributed to hereditary cancer syndromes. A tremendous progress has been made over the last decade in the evaluation and management of these syndromes. Read More

Front Oncol 2022 28;12:849004. Epub 2022 Mar 28.

Department of Molecular Genetics, National Institute of Oncology, Budapest, Hungary.

Since the introduction of next-generation sequencing, the frequency of germline pathogenic variants and the number of cases with unusual clinical presentations have been increasing. This has led to the expansion of the classical Li-Fraumeni syndrome concept to a wider cancer predisposition syndrome designated as the Li-Fraumeni spectrum. Here, we present a case with a malignant, metastatic perivascular epithelioid cell tumor (PEComa) of the thigh muscle and a sinonasal carcinoma harboring a novel germline splice mutation (NM_000546. Read More

Mol Syndromol 2022 Feb 4;13(2):123-131. Epub 2021 Nov 4.

Department of Medical Genetics, Faculty of Medicine, Ataturk University, Erzurum, Turkey.

A hereditary cancer syndrome is a genetic predisposition to cancer caused by a germline mutation in cancer-related genes. Identifying the disease-causing variant is important for both the patient and relatives at risk in cancer families because this could be a guide in treatment and secondary cancer prevention. In this study, hereditary cancer panel harboring cancer-related genes was performed on MiSeq Illumina NGS system from peripheral blood samples. Read More

Cancers (Basel) 2022 Mar 23;14(7). Epub 2022 Mar 23.

Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK.

The concept of the pre-cancerous niche applies the 'seed and soil' theory of metastasis to the initial process of carcinogenesis. TP53 is at the nexus of this process and, in the context of Li-Fraumeni Syndrome (LFS), is a key determinant of the conditions in which cancers are formed and progress. Important factors in the creation of the pre-cancerous niche include disrupted tissue homeostasis, cellular metabolism and chronic inflammation. Read More

Pediatr Radiol 2022 Jun 8;52(7):1283-1295. Epub 2022 Apr 8.

Department of Medical Imaging, The Hospital for Sick Children University of Toronto, 555 University Ave., 2nd floor, Toronto, ON, M5G1X8, Canada.

Background: The Toronto protocol for cancer surveillance in children with Li-Fraumeni syndrome has been adopted worldwide.

Objective: To assess the diagnostic accuracy of the imaging used in this protocol.

Materials And Methods: We conducted a blinded retrospective review of imaging modalities in 31 pediatric patients. Read More

Eur Radiol Exp 2022 04 7;6(1):17. Epub 2022 Apr 7.

Institut National de la Santé et de la Recherche Médicale, U1296 Radiations Defense, Health and Environment Centre Léon-Bérard, 69008, Lyon, France.

Background: While computed tomography (CT) exams are the major cause of medical exposure to ionising radiation, the radiation-induced risks must be documented. We investigated the impact of the cellular models and individual factor on the deoxyribonucleic acid double-strand breaks (DSB) recognition and repair in human skin fibroblasts and brain astrocytes exposed to current head CT scan conditions.

Method: Nine human primary fibroblasts and four human astrocyte cell lines with different levels of radiosensitivity/susceptibility were exposed to a standard head CT scan exam using adapted phantoms. Read More

Front Oncol 2022 16;12:836937. Epub 2022 Mar 16.

Oncology Center, Hospital Sírio-Libanês, São Paulo, Brazil.

Breast cancer (BC) is the most prevalent malignancy in women with Li-Fraumeni syndrome (LFS). The literature on BC in LFS is limited due to its rarity worldwide. A founder pathogenic variant (c. Read More

Soc Sci Med 2022 05 17;301:114905. Epub 2022 Mar 17.

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

Introduction: Experiences of illness change the physical body and embodiments, or the ways in which the world and the self are known through the body. When illness is anticipated, such as with inherited cancer predisposition syndromes, risk becomes embodied and shared in family groups. Embodied risk is experienced whether or not symptoms have manifested. Read More

Biochimie 2022 Jul 1;198:141-154. Epub 2022 Apr 1.

Laboratório de Genômica Estrutural e Funcional, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil; Programa de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia, UFRGS, Porto Alegre, Brazil. Electronic address:

Li-Fraumeni and Li-Fraumeni-like syndromes (LFS/LFL) are hereditary cancer predisposition disorders associated with germline mutations in the TP53 tumor suppressor gene. Here, we stably expressed LFS/LFL-associated p53 mutants R337H and G245S in p53-null H1299 cells to study their cellular and molecular effects. Mutant proteins showed distinct oligomerization states and opposing effects on cell proliferation and viability. Read More

Ann Oncol 2022 Jun 23;33(6):578-592. Epub 2022 Mar 23.

Center for Childhood Cancer and Blood Diseases, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, USA; Molecular, Cellular and Developmental Biology Graduate Program and The Center for RNA Biology, The Ohio State University, Columbus, USA. Electronic address:

Background: Compared with adult cancers, pediatric cancers are uniquely characterized by a genomically stable landscape and lower tumor mutational burden. Alternative splicing, however, a global cellular process that produces different messenger RNA/protein isoforms from a single messenger RNA transcript, has been increasingly implicated in the development of pediatric cancers.

Design: We review the current literature on the role of alternative splicing in adult cancer, cancer predisposition syndromes, and pediatric cancers. Read More

Cancer Res 2022 May;82(10):1926-1936

Department of Genetics, The University of Texas MD Anderson Cancer Center, UT Health Graduate School of Biomedical Sciences, Houston, Texas.

The majority of TP53 missense mutations identified in cancer patients are in the DNA-binding domain and are characterized as either structural or contact mutations. These missense mutations exhibit inhibitory effects on wild-type p53 activity. More importantly, these mutations also demonstrate gain-of-function (GOF) activities characterized by increased metastasis, poor prognosis, and drug resistance. Read More

Exp Ther Med 2022 Apr 16;23(4):287. Epub 2022 Feb 16.

Department of Endocrinology, 'Carol Davila' University of Medicine and Pharmacy, 050474 Bucharest, Romania.

Adrenocortical carcinoma (adrenal cortex-derived cancer), an orphan malignancy, is a very aggressive disease that affects both adults and children with an annual incidence of 1-2 adult and 0.2-0.38 pediatric cases/million (in the pediatric population it represents 0. Read More

Cancer Genet 2022 06 3;264-265:29-32. Epub 2022 Mar 3.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, United States; Department of Pediatrics, Baylor College of Medicine, Houston, TX, United States; Texas Children's Cancer Center, Texas Children's Hospital, Houston, TX, United States. Electronic address:

Li-Fraumeni syndrome, caused by germline pathogenic variants in TP53, results in susceptibility to multiple cancers. Variants of uncertain significance (VUS) and reclassification of variants over time pose management concerns given improved survival with cancer surveillance for LFS patients. We describe the experience of TP53 variant reclassification at a pediatric cancer center. Read More

Eur Radiol Exp 2022 03 17;6(1):14. Epub 2022 Mar 17.

Institut National de la Santé et de la Recherche Médicale, U1296, « Radiations: Defense, Health and Environment », Bât Cheney A 28 Rue Laennec Centre Léon-Bérard, 69008, Lyon, France.

Background: While computed tomography (CT) exams are the major cause of medical exposure to ionising radiation, there is increasing evidence that the potential radiation-induced risks must be documented. We investigated the impact of cellular models and individual factor on the deoxyribonucleic acid double-strand breaks (DSB) recognition and repair in human fibroblasts and mammary epithelial cells exposed to current chest CT scan conditions.

Method: Twelve human primary fibroblasts and four primary human mammary epithelial cell lines with different levels of radiosensitivity/susceptibility were exposed to a standard chest CT scan exam using adapted phantoms. Read More

Am J Dermatopathol 2022 04;44(4):e37-e38

Department of Dermatology, University of Pennsylvania, Philadelphia, PA.

Am J Dermatopathol 2022 04;44(4):312-313

Department of Dermatology, University of Pennsylvania, Philadelphia, PA.

Quant Imaging Med Surg 2022 Mar;12(3):2189-2192

Department of Radiology, Shenzhen Children's Hospital, Shenzhen, China.

Best Pract Res Clin Obstet Gynaecol 2022 Jun 31;82:3-11. Epub 2022 Jan 31.

University of Iowa Hospitals and Clinics, Department of Obstetrics & Gynecology, 200 Hawkins Drive, Iowa City, IA, USA. Electronic address:

The risk of developing breast cancer is multifactorial and, at times, modifiable. However, the risk imposed by family history and hereditary pathogenic variants in a person's genetic code is, at present, an important fixed variable. Therefore, it is imperative to identify patients at risk for hereditary breast cancer and to understand the current evidence-based approach to the management of that risk. Read More