Search Our Scientific Publications & Authors

J Clin Invest 2021 May 13. Epub 2021 May 13.

Josep Carreras Leukemia Research Institute-Campus Clinic, University of Barcelona, Barcelona, Spain.

B-cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer. As predicated by its prenatal origin, infant B-ALL (iB-ALL) shows an exceptionally silent DNA mutational landscape, suggesting that alternative epigenetic mechanisms may substantially contribute to its leukemogenesis. Here, we have integrated genome-wide DNA methylome and transcriptome data from 69 patients with de novo MLL-rearranged (MLLr) and non-MLLr iB-ALL leukemias uniformly treated according to Interfant-99/06 protocol. Read More

Transl Oncol 2021 May 8;14(8):101114. Epub 2021 May 8.

Department of Genetics, Albert Einstein College of Medicine, 1300 Morris Park Avenue Ullmann 813 Bronx, NY 10461, United States; Department of Pediatrics, Albert Einstein College of Medicine, United States.

Across many cancer types in adults, upregulation of the nuclear-to-cytoplasmic transport protein Exportin-1 (XPO1) correlates with poor outcome and responsiveness to selinexor, an FDA-approved XPO1 inhibitor. Similar data are emerging in childhood cancers, for which selinexor is being evaluated in early phase clinical studies. Using proteomic profiling of primary tumor material from patients with high-risk neuroblastoma, as well as gene expression profiling from independent cohorts, we have demonstrated that XPO1 overexpression correlates with poor patient prognosis. Read More

Pediatr Dev Pathol 2021 May 10:10935266211015558. Epub 2021 May 10.

Department of Pathology and Laboratory Medicine, Cumming School of Medicine, Calgary, Alberta, Canada.

Background: Pediatric fibroblastic/myofibroblastic tumors (PFMTs) can be challenging to definitively classify. Large case series or diagnostic updates have not been recently published despite identification of molecular alterations that could improve diagnostic accuracy. Our review of the literature found that over two-thirds of the more than 30 types of PFMTs harbor recurrent molecular alterations. Read More

Environ Int 2021 May 6;155:106613. Epub 2021 May 6.

Department of Public Health, Aarhus University, Aarhus, Denmark.

Background: There is limited evidence that nitrate, a common contaminant in drinking water, increases the risk of childhood cancers. Our objective was to examine this association in Denmark.

Methods: We conducted a nationwide case-control study based on all singletons liveborn to Danish-born parents from 1991 to 2015 (N = 1,219,140) that included 596 leukemias, 180 lymphomas, and 310 central nervous system cancers (CNC) who were ≤15 years of age at diagnosis and were identified from the Danish Cancer Registry. Read More

J Immunother Cancer 2021 May;9(5)

Department of Paediatric Haematology and Oncology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy

Background: Pediatric high-grade gliomas (pHGGs) are among the most common and incurable malignant neoplasms of childhood. Despite aggressive, multimodal treatment, the outcome of children with high-grade gliomas has not significantly improved over the past decades, prompting the development of innovative approaches.

Methods: To develop an effective treatment, we aimed at improving the suboptimal antitumor efficacy of oncolytic adenoviruses (OAs) by testing the combination with a gene-therapy approach using a bispecific T-cell engager (BiTE) directed towards the erythropoietin-producing human hepatocellular carcinoma A2 receptor (EphA2), conveyed by a replication-incompetent adenoviral vector (EphA2 adenovirus (EAd)). Read More

Cancer Genet 2021 Apr 23;256-257:77-80. Epub 2021 Apr 23.

Manchester Academic Health Science Centre; Department of Paediatric Haematology and Oncology, Royal Manchester Children's Hospital, Manchester NHS Foundation Trust Manchester, UK; Stem Cell and Leukaemia Proteomics Laboratory, Faculty of Medical and Human Sciences, Division of Cancer Studies, University of Manchester, UK; Department of Paediatric and Adolescent Oncology, The Christie NHS Foundation Trust, Manchester, UK. Electronic address:

Pathogenic germ-line variants in GATA2 (GATA2-deficiency) can cause childhood myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML), and can be associated with distinct clinical syndromic features. However, penetrance and genotype-phenotype correlations are incompletely understood. Here we report on the clinically diverse features of three siblings affected by GATA2c. Read More

J Racial Ethn Health Disparities 2021 May 4. Epub 2021 May 4.

Cardiovascular Section, Social and Behavioral Research Branch, National Human Genome Research Institute, National Institutes of Health, 10 Center Drive, Room 7N316 MSC 1644, Bethesda, MD, USA.

Purpose: We examined if childhood socioeconomic status (SES) was related to adult leucocyte telomere length (TL) using the data of 361 African American (AA) participants from the GENE-FORECAST Study. We also assessed the mediating role of behavioral and psychosocial factors in the association between childhood SES and adult TL.

Methods: Childhood SES was assessed individually by using participant's mother's education and occupation, father's education and occupation, parental home ownership, and family structure. Read More

mSystems 2021 May 4;6(3). Epub 2021 May 4.

Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA

Coronavirus disease 2019 (COVID-19) has caused global disruption and a significant loss of life. Existing treatments that can be repurposed as prophylactic and therapeutic agents may reduce the pandemic's devastation. Emerging evidence of potential applications in other therapeutic contexts has led to the investigation of dietary supplements and nutraceuticals for COVID-19. Read More

Oncogene 2021 May 4. Epub 2021 May 4.

Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Box 582, Biomedical Center, Uppsala University, Uppsala, Sweden.

Activation of the transforming growth factor β (TGFβ) pathway modulates the expression of genes involved in cell growth arrest, motility, and embryogenesis. An expression screen for long noncoding RNAs indicated that TGFβ induced mir-100-let-7a-2-mir-125b-1 cluster host gene (MIR100HG) expression in diverse cancer types, thus confirming an earlier demonstration of TGFβ-mediated transcriptional induction of MIR100HG in pancreatic adenocarcinoma. MIR100HG depletion attenuated TGFβ signaling, expression of TGFβ-target genes, and TGFβ-mediated cell cycle arrest. Read More

Tumour Biol 2021 ;43(1):11-26

Institute of Anatomy II, Department of Neuroanatomy, University of Duisburg-Essen, Medical Faculty, Essen, Germany.

Background: Retinoblastoma (RB) is the most common childhood eye cancer. Chemotherapeutic drugs such as etoposide used in RB treatment often cause massive side effects and acquired drug resistances. Dysregulated genes and miRNAs have a large impact on cancer progression and development of chemotherapy resistances. Read More

NPJ Precis Oncol 2021 Apr 30;5(1):34. Epub 2021 Apr 30.

Department of Paediatric Oncology Comprehensive Cancer Centre, King Fahad Medical City, Riyadh, Kingdom of Saudi Arabia.

Brain tumors are the leading cause of childhood cancer-related deaths. Similar to adult brain tumors, pediatric brain tumors are classified based on histopathological evaluations. However, pediatric brain tumors are often histologically inconsistent with adult brain tumors. Read More

Int J Mol Sci 2021 Apr 12;22(8). Epub 2021 Apr 12.

Laboratorio Cellule Staminali Post-Natali e Terapie Cellulari, IRCCS Istituto Giannina Gaslini, 16147 Genova, Italy.

The long-underestimated role of extracellular vesicles in cancer is now reconsidered worldwide by basic and clinical scientists, who recently highlighted novel and crucial activities of these moieties. Extracellular vesicles are now considered as king transporters of specific cargoes, including molecular components of parent cells, thus mediating a wide variety of cellular activities both in normal and neoplastic tissues. Here, we discuss the multifunctional activities and underlying mechanisms of extracellular vesicles in neuroblastoma, the most frequent common extra-cranial tumor in childhood. Read More

Int J Mol Sci 2021 Apr 10;22(8). Epub 2021 Apr 10.

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Central nervous system tumor with BCL6-corepressor internal tandem duplication (CNS-BCOR ITD) is a malignant entity characterized by recurrent alterations in exon 15 encoding the essential binding domain for the polycomb repressive complex (PRC). In contrast to deletion or truncating mutations seen in other tumors, BCOR expression is upregulated in CNS-BCOR ITD, and a distinct oncogenic mechanism has been suggested. However, the effects of this change on the biology of neuroepithelial cells is poorly understood. Read More

Cancers (Basel) 2021 Apr 14;13(8). Epub 2021 Apr 14.

Institute of Human Genetics, Medical Faculty, University Duisburg-Essen, 45122 Essen, Germany.

Retinoblastoma and other eye tumors in childhood are rare diseases. Many eye tumors are the first signs of a genetic tumor predisposition syndrome and the affected children carry a higher risk of developing other cancers later in life. Clinical and genetic data of all children with eye tumors diagnosed between 2013-2018 in Germany and Austria were collected in a multicenter prospective observational study. Read More

Cancers (Basel) 2021 Apr 21;13(9). Epub 2021 Apr 21.

Division of Hematology/Oncology, UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA 15224, USA.

Hepatoblastoma (HB), the most common childhood liver cancer, is associated with seven distinct histologic subtypes and variable degrees of clinical aggressiveness and presentation. Yet it is among the least genomically altered tumors known, with about half of HBs showing mutation and/or dysregulation of the Wnt/β-catenin and Hippo pathways. This raises the question of how this mutational simplicity can generate such biological and histologic complexity. Read More

Cancers (Basel) 2021 Apr 9;13(8). Epub 2021 Apr 9.

Children's Cancer Institute, Lowy Cancer Research Centre, UNSW Australia, PO Box 81, Randwick, NSW 2031, Australia.

Ornithine decarboxylase (ODC1), a critical regulatory enzyme in polyamine biosynthesis, is a direct transcriptional target of MYCN, amplification of which is a powerful marker of aggressive neuroblastoma. A single nucleotide polymorphism (SNP), G316A, within the first intron of , results in genotypes wildtype GG, and variants AG/AA. CRISPR-cas9 technology was used to investigate the effects of AG clones from wildtype -amplified SK-N-BE(2)-C cells and the effect of the SNP on MYCN binding, and promoter activity was investigated using EMSA and luciferase assays. Read More

Diagnostics (Basel) 2021 Apr 2;11(4). Epub 2021 Apr 2.

Department of Onco-Hematology and Cell and Gene Therapy, Bambino Gesù Children's Hospital (IRCCS), 00165 Rome, Italy.

Brain tumors are the most common solid neoplasms of childhood. They are frequently reported in children with Neurofibromatosis type 1 (NF1). The most frequent central nervous system malignancies described in NF1 are optic pathway gliomas and brainstem gliomas. Read More

Cancers (Basel) 2021 Apr 2;13(7). Epub 2021 Apr 2.

Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Background: Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in Africa and is linked to () malaria infection, one of the most common and deadly childhood infections in Africa; however, the role of genetic diversity is unclear. A potential role of genetic diversity in eBL has been suggested by a correlation of age-specific patterns of eBL with the complexity of infection in Ghana, Uganda, and Tanzania, as well as a finding of significantly higher genetic diversity, based on a sensitive molecular barcode assay, in eBL cases than matched controls in Malawi. We examined this hypothesis by measuring diversity in serine repeat antigen-5 (), an antigenic target of blood-stage immunity to malaria, among 200 eBL cases and 140 controls, all polymerase chain reaction (PCR)-positive, in Malawi. Read More

J Clin Med 2021 Apr 1;10(7). Epub 2021 Apr 1.

Department of Pediatrics and Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

Rhabdomyosarcoma is the most common soft tissue sarcoma diagnosed in children and adolescents. Patients that are diagnosed with advanced or relapsed disease have exceptionally poor outcomes. The Children's Oncology Group (COG) convened a rhabdomyosarcoma new agent task force in 2020 to systematically evaluate novel agents for inclusion in phase 2 or phase 3 clinical trials for patients diagnosed with rhabdomyosarcoma, following a similar effort for Ewing sarcoma. Read More

Eur J Hum Genet 2021 Apr 26. Epub 2021 Apr 26.

Canadian Centre for Applied Research in Cancer Control, BC Cancer, Vancouver, Canada.

Genomic testing is becoming routine for diagnosing rare childhood genetic disease. Evidence underlying sustainable implementation is limited, focusing on short-term endpoints such as diagnostic yield, unable to fully characterize patient and family valued outcomes. Although genomic testing is becoming widely available, evidentiary and outcomes uncertainty persist as key challenges for implementation. Read More

Cancer Genet 2021 Apr 10;256-257:51-56. Epub 2021 Apr 10.

Department/Center of Hematology-oncology, Diagnostic and Treatment Center for Childhood Leukemia of Zhejiang Province, Children's Hospital of Zhejiang University School of Medicine, National Medical Research Center for Child Health, #57 Zhuganxiang Road, Yan-an Street, Hangzhou 310003, China. Electronic address:

In the study of acute myeloid leukemia (AML), TLS-ERG (also called FUS-ERG or TLS/FUS-ERG) was found to be closely associated with extramedullary disease (EMD), with very poor prognosis. However, the occurrence of TLS-ERG in acute lymphoblastic leukemia (ALL) is very rare. Till date, only 20 cases of ALL with TLS-ERG gene have been reported, of which six are children. Read More

Science 2021 May 22;372(6543). Epub 2021 Apr 22.

Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.

The 1986 Chernobyl nuclear power plant accident increased papillary thyroid carcinoma (PTC) incidence in surrounding regions, particularly for radioactive iodine (I)-exposed children. We analyzed genomic, transcriptomic, and epigenomic characteristics of 440 PTCs from Ukraine (from 359 individuals with estimated childhood I exposure and 81 unexposed children born after 1986). PTCs displayed radiation dose-dependent enrichment of fusion drivers, nearly all in the mitogen-activated protein kinase pathway, and increases in small deletions and simple/balanced structural variants that were clonal and bore hallmarks of nonhomologous end-joining repair. Read More

Comput Methods Programs Biomed 2021 Apr 9;205:106093. Epub 2021 Apr 9.

Department of Human Genetics, KU Leuven, Leuven, Belgium; Big Data Institute and Nuffield Department of Women's & Reproductive Health, University of Oxford, Oxford, United Kingdom.

Background and Objective; Genetic risk factors for childhood cancer may also influence facial morphology. 3D photography can be used in the recognition of differences in face shape among individuals. In previous research, 3D facial photography was used to identify increased facial asymmetry and greater deviation from normal facial morphology in a group of individuals with distinct morphological features who had childhood cancer compared to healthy controls. Read More

Cell Rep 2021 Apr;35(3):109010

Institute of Cancer and Genomic Sciences, College of Medicine and Dentistry, University of Birmingham, Edgbaston, Birmingham B152TT, UK. Electronic address:

Acute myeloid leukemia (AML) is caused by recurrent mutations in members of the gene regulatory and signaling machinery that control hematopoietic progenitor cell growth and differentiation. Here, we show that the transcription factor WT1 forms a major node in the rewired mutation-specific gene regulatory networks of multiple AML subtypes. WT1 is frequently either mutated or upregulated in AML, and its expression is predictive for relapse. Read More

Hormones (Athens) 2021 Apr 20. Epub 2021 Apr 20.

Division of Pediatrics, S. Chiara General Hospital, Largo Medaglie d'oro, 9, 38122, Trento, Italy.

Introduction: The PI3K/AKT/mTOR signaling pathway is important for the regulation of multiple biological processes, including cellular growth and glucose metabolism. Defects of the PI3K/AKT/mTOR signaling pathway are not usually considered among the genetic causes of recurrent hypoglycemia in childhood. However, accumulating evidence links hypoglycemia with defects of this pathway. Read More

Leukemia 2021 May 16;35(5):1485-1489. Epub 2021 Apr 16.

Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.

Cancer Gene Ther 2021 Apr 16. Epub 2021 Apr 16.

Division of Pediatric Surgery, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.

Hepatoblastoma remains one of the most difficult childhood tumors to treat and is alarmingly understudied. We previously demonstrated that Proviral Insertion site in Maloney murine leukemia virus (PIM) kinases, specifically PIM3, are overexpressed in human hepatoblastoma cells and function to promote tumorigenesis. We aimed to use CRISPR/Cas9 gene editing with dual gRNAs to introduce large inactivating deletions in the PIM3 gene and achieve stable PIM3 knockout in the human hepatoblastoma cell line, HuH6. Read More

Leukemia 2021 May;35(5):1527

Department of Pediatrics and the Center for Childhood Cancer Research, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Nat Commun 2021 04 12;12(1):2148. Epub 2021 Apr 12.

Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Deregulation of chromatin modifiers plays an essential role in the pathogenesis of medulloblastoma, the most common paediatric malignant brain tumour. Here, we identify a BMI1-dependent sensitivity to deregulation of inositol metabolism in a proportion of medulloblastoma. We demonstrate mTOR pathway activation and metabolic adaptation specifically in medulloblastoma of the molecular subgroup G4 characterised by a BMI1;CHD7 signature and show this can be counteracted by IP6 treatment. Read More

Int J Lab Hematol 2021 Apr 12. Epub 2021 Apr 12.

Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.

Introduction: The lymphoid enhancer factor 1 (LEF1) is a DNA-binding transcription factor that functions in the Wnt signaling pathway. Increased LEF1 activity is associated with progression of several types of cancer including leukemia. Here, we investigated LEF1 isoform expression and genomic variations in acute lymphoblastic leukemia (ALL). Read More