Search Our Scientific Publications & Authors

Cancers (Basel) 2020 May 19;12(5). Epub 2020 May 19.

Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, 2100 Copenhagen, Denmark.

Symptomatic venous thromboembolism (VTE) occurs in five percent of children treated for acute lymphoblastic leukemia (ALL), but whether a genetic predisposition exists across different ALL treatment regimens has not been well studied.

Methods: We undertook a genome-wide association study (GWAS) meta-analysis for VTE in consecutively treated children in the Nordic/Baltic acute lymphoblastic leukemia 2008 (ALL2008) cohort and the Australian Evaluation of Risk of ALL Treatment-Related Side-Effects (ERASE) cohort. A total of 92 cases and 1481 controls of European ancestry were included. Read More

Elife 2020 May 20;9. Epub 2020 May 20.

Departments of Biochemistry and Medicine, Stanford University School of Medicine, Stanford, United States.

R-spondins (RSPOs) amplify WNT signaling during development and regenerative responses. We previously demonstrated that RSPOs 2 and 3 potentiate WNT/β-catenin signaling in cells lacking leucine-rich repeat-containing G-protein coupled receptors (LGRs) 4, 5 and 6 (Lebensohn and Rohatgi, 2018). We now show that heparan sulfate proteoglycans (HSPGs) act as alternative co-receptors for RSPO3 using a combination of ligand mutagenesis and ligand engineering. Read More

Nat Neurosci 2020 May 18. Epub 2020 May 18.

Tumor Initiation & Maintenance Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.

Many immunotherapies act by enhancing the ability of cytotoxic T cells to kill tumor cells. Killing depends on T cell recognition of antigens presented by class I major histocompatibility complex (MHC-I) proteins on tumor cells. In this study, we showed that medulloblastomas lacking the p53 tumor suppressor do not express surface MHC-I and are therefore resistant to immune rejection. Read More

Mol Genet Genomic Med 2020 May 17:e1302. Epub 2020 May 17.

Department of Pediatrics, MRC Oulu, PEDEGO Research Unit, University of Oulu and Oulu University Hospital, Oulu, Finland.

Background: Medulloblastomas (MBs) are a heterogeneous group of childhood brain tumors with four consensus subgroups, namely MB , MB , MB , and MB , representing the second most common type of pediatric brain cancer after high-grade gliomas. They suffer from a high prevalence of genetic predisposition with up to 20% of MB caused by germline mutations in only six genes. However, the spectrum of germline mutations in MB remains incomplete. Read More

iScience 2020 May 29;23(5):101103. Epub 2020 Apr 29.

Genetics Branch, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address:

Core regulatory transcription factors (CR TFs) establish enhancers with logical ordering during embryogenesis and development. Here we report that in fusion-positive rhabdomyosarcoma, a cancer of the muscle lineage, the chief oncogene PAX3-FOXO1 is driven by a translocated FOXO1 super enhancer (SE) restricted to a late stage of myogenesis. Using chromatin conformation capture techniques, we demonstrate that the extensive FOXO1 cis-regulatory domain interacts with PAX3. Read More

Sci Rep 2020 May 15;10(1):8079. Epub 2020 May 15.

Department of Human Genetics, McGill University, Montréal, Québec, Canada.

Childhood acute lymphoblastic leukemia (cALL) is the most common pediatric cancer. It is characterized by bone marrow lymphoid precursors that acquire genetic alterations, resulting in disrupted maturation and uncontrollable proliferation. More than a dozen molecular subtypes of variable severity can be used to classify cALL cases. Read More

Front Pediatr 2020 28;8:189. Epub 2020 Apr 28.

Department of Ecology and Evolutionary Biology, University of California, Irvine, Irvine, CA, United States.

A new hypothesis suggests that somatic genome remodeling during normal development can cause mutations that explain many early onset cancers in children and adults. Read More

Sci Rep 2020 May 14;10(1):7974. Epub 2020 May 14.

Department of Social Research, University of Helsinki, Helsinki, 00014, Finland.

Genetic factors explain a major proportion of human height variation, but differences in mean stature have also been found between socio-economic categories suggesting a possible effect of environment. By utilizing a classical twin design which allows decomposing the variation of height into genetic and environmental components, we tested the hypothesis that environmental variation in height is greater in offspring of lower educated parents. Twin data from 29 cohorts including 65,978 complete twin pairs with information on height at ages 1 to 69 years and on parental education were pooled allowing the analyses at different ages and in three geographic-cultural regions (Europe, North America and Australia, and East Asia). Read More

Leukemia 2020 May 14. Epub 2020 May 14.

Paediatric Hematology & Oncology, University Hospital Münster, Münster, Germany.

Antioxid Redox Signal 2020 May 10. Epub 2020 May 10.

Research Centre, CHU Ste-Justine, Nutrition, Université de Montréal, 3175, Ste-Catherine Road, Montreal, Quebec, Canada, H3T 1C5.

Significance: Survivors of pediatric cancers have a high risk of developing side effects after the end of their treatments. Many potential factors have been associated with the onset of cardiometabolic disorders (CMD), including cancer disease itself, chemotherapy, hormonal treatment, radiotherapy and genetics. However, the precise etiology and underlying mechanisms of these long-term complications are poorly understood. Read More

Pediatr Blood Cancer 2020 May 8:e28388. Epub 2020 May 8.

Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.

Background: Cardiac autonomic dysfunction (CAD) is possible following treatment for childhood cancer. The aims of our analyses were to compare the prevalence of CAD between adult survivors of childhood acute lymphoblastic leukemia and controls, compare exercise response among survivors with and without CAD, and identify treatment-related risk factors for CAD.

Procedure: Participants were treated for childhood acute lymphoblastic leukemia at St. Read More

Eur J Epidemiol 2020 May 7. Epub 2020 May 7.

Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, 1440 Canal St, Suite 1724, New Orleans, LA, 70112, USA.

Epidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study, we evaluated the causal association of low birthweight with adulthood hypertension following a standard analytic protocol using the study-level data of 183,433 participants from 60 studies (CHARGE-BIG consortium), as well as that with blood pressure using publicly available summary-level genome-wide association data from EGG consortium of 153,781 participants, ICBP consortium and UK Biobank cohort together of 757,601 participants. Read More

Blood Cancer J 2020 May 5;10(5):51. Epub 2020 May 5.

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

Cell J 2021 Jan 27;22(4):556-564. Epub 2020 Apr 27.

Department of Haematology, Tarbiat Modares University, Tehran, Iran.

Objective: Neuroblastoma (NB) is one of the frequently observed malignant solid tumors of childhood and infancy, accounting for 15% of pediatric cancer deaths. Recently, the approach of differentiation therapy has shown considerable promise in effective treatment of NB patients. MiR-124 belongs to the nervous system-specific miRNAs that is increased during neuronal differentiation and may be one of the potential therapeutic targets for the treatment of NB. Read More

Diabetes Care 2020 Apr 28. Epub 2020 Apr 28.

Medical Research Council Integrative Epidemiology Unit at the University of Bristol, Bristol, U.K.

Objective: Type 2 diabetes develops for many years before diagnosis. We aimed to reveal early metabolic features characterizing liability to adult disease by examining genetic liability to adult type 2 diabetes in relation to metabolomic traits across early life.

Research Design And Methods: Up to 4,761 offspring from the Avon Longitudinal Study of Parents and Children were studied. Read More

Cancer 2020 Apr 22. Epub 2020 Apr 22.

Division of Clinical Genetics, Memorial Sloan Kettering Cancer Center, New York, New York.

Background: Constitutional or somatic mosaic epimutations are increasingly recognized as a mechanism of gene dysregulation resulting in cancer susceptibility. Beckwith-Wiedemann syndrome is the cancer predisposition syndrome most commonly associated with epimutation and is extremely variable in its phenotypic presentation, which can include isolated tumors. Because to the authors' knowledge large-scale germline DNA sequencing studies have not included methylation analysis, the percentage of pediatric cancer predisposition that is due to epimutations is unknown. Read More

Blood 2020 Apr;135(17):1438-1446

Leukaemia Research Cytogenetics Group, Wolfson Childhood Cancer Centre, Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.

Risk stratification is essential for the delivery of optimal treatment in childhood acute lymphoblastic leukemia. However, current risk stratification algorithms dichotomize variables and apply risk factors independently, which may incorrectly assume identical associations across biologically heterogeneous subsets and reduce statistical power. Accordingly, we developed and validated a prognostic index (PIUKALL) that integrates multiple risk factors and uses continuous data. Read More

Br J Haematol 2020 Apr 21. Epub 2020 Apr 21.

Stem Cell Laboratory, Bone Marrow Unit (INCA), Rio de Janeiro, Brazil.

Genes Chromosomes Cancer 2020 Apr 19. Epub 2020 Apr 19.

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

In recent years, a subgroup of B-cell precursor acute lymphoblastic leukemia (BCP ALL) without an established abnormality ("B-other") has been shown to be characterized by rearrangements of ABL1, ABL2, CSF1R, or PDGFRB (a.k.a. Read More

Acta Neuropathol 2020 Jun 17;139(6):1071-1088. Epub 2020 Apr 17.

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

Brain tumors are the most common solid tumors of childhood, and the genetic drivers and optimal therapeutic strategies for many of the different subtypes remain unknown. Here, we identify that bithalamic gliomas harbor frequent mutations in the EGFR oncogene, only rare histone H3 mutation (in contrast to their unilateral counterparts), and a distinct genome-wide DNA methylation profile compared to all other glioma subtypes studied to date. These EGFR mutations are either small in-frame insertions within exon 20 (intracellular tyrosine kinase domain) or missense mutations within exon 7 (extracellular ligand-binding domain) that occur in the absence of accompanying gene amplification. Read More

Cell 2020 Apr;181(2):236-249

Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Present address: Foundation Medicine, Cambridge, MA 02141, USA.

Crucial transitions in cancer-including tumor initiation, local expansion, metastasis, and therapeutic resistance-involve complex interactions between cells within the dynamic tumor ecosystem. Transformative single-cell genomics technologies and spatial multiplex in situ methods now provide an opportunity to interrogate this complexity at unprecedented resolution. The Human Tumor Atlas Network (HTAN), part of the National Cancer Institute (NCI) Cancer Moonshot Initiative, will establish a clinical, experimental, computational, and organizational framework to generate informative and accessible three-dimensional atlases of cancer transitions for a diverse set of tumor types. Read More

Nature 2020 04 1;580(7803):396-401. Epub 2020 Apr 1.

Hopp Children's Cancer Center Heidelberg (KiTZ), Heidelberg, Germany.

Cancer genomics has revealed many genes and core molecular processes that contribute to human malignancies, but the genetic and molecular bases of many rare cancers remains unclear. Genetic predisposition accounts for 5 to 10% of cancer diagnoses in children, and genetic events that cooperate with known somatic driver events are poorly understood. Pathogenic germline variants in established cancer predisposition genes have been recently identified in 5% of patients with the malignant brain tumour medulloblastoma. Read More

Pediatr Blood Cancer 2020 Jun 15;67(6):e28255. Epub 2020 Apr 15.

Department of Medical Biology, Medical University of Plovdiv, Plovdiv, Bulgaria.

The first observations of altered metabolism in malignant cells were made nearly 100 years ago and therapeutic strategies targeting cell metabolism have been in clinical use for several decades.  In this review, we summarize our current understanding of cell metabolism dysregulation in childhood acute lymphoblastic leukemia (cALL). Reprogramming of cellular bioenergetic processes can be expected in the three distinct stages of cALL: at diagnosis, during standard chemotherapy, and in cases of relapse. Read More

Cancer Res 2020 Apr 14. Epub 2020 Apr 14.

Cancer Center, Texas Tech University Health Sciences Center School of Medicine

Neuroblastoma is a childhood cancer with heterogeneous clinical outcomes. To comprehensively assess the impact of telomere maintenance mechanism (TMM) on clinical outcomes in high-risk neuroblastoma, we integrated the C-circle assay (a marker for alternative lengthening of telomeres (ALT)), TERT mRNA expression by RNA sequencing, whole genome/exome sequencing, and clinical co-variates in 134 neuroblastoma patient samples at diagnosis. In addition, we assessed TMM in neuroblastoma cell lines (n=104) and PDX (n=28). Read More

Clin Genet 2020 Jun 20;97(6):890-901. Epub 2020 Apr 20.

Department of Pediatrics, Amsterdam UMC, Amsterdam, The Netherlands.

Primrose syndrome (PS; MIM# 259050) is characterized by intellectual disability (ID), macrocephaly, unusual facial features (frontal bossing, deeply set eyes, down-slanting palpebral fissures), calcified external ears, sparse body hair and distal muscle wasting. The syndrome is caused by de novo heterozygous missense variants in ZBTB20. Most of the 29 published patients are adults as characteristics appear more recognizable with age. Read More

J Glob Health 2020 Jun;10(1):010801

Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.

Background: In China, childhood asthma prevalence showed a remarkable increase in the past decades. An updated epidemiological assessment of childhood asthma in China with a focus on prevalence and time trends is required.

Methods: We systematically searched three main Chinese databases and one English database to identify epidemiological studies of the prevalence of childhood asthma in China. Read More

J Glob Health 2020 Jun;10(1):010404

Centre for Molecular Epidemiology and Translational Research, Institute for Global Health, University College London, London, UK.

Background: Epstein-Barr virus (EBV) is an important human pathogen; it infects >90% people globally and is linked to infectious mononucleosis and several types of cancer. Vaccines against EBV are in development. In this study we present the first systematic review of the literature on risk factors for EBV infection, and discuss how they differ between settings, in order to improve our understanding of EBV epidemiology and aid the design of effective vaccination strategies. Read More

Bone 2020 Jul 3;136:115353. Epub 2020 Apr 3.

Department of Pediatrics, University of Minnesota, United States of America; Department of Genetics, Cell Biology and Development, University of Minnesota, United States of America; Center for Genome Engineering, University of Minnesota, United States of America; Masonic Cancer Center, University of Minnesota, United States of America. Electronic address:

Osteosarcoma (OSA) is a heterogeneous and aggressive solid tumor of the bone. We recently identified the colony stimulating factor 1 receptor (Csf1r) gene as a novel driver of osteosarcomagenesis in mice using the Sleeping Beauty (SB) transposon mutagenesis system. Here, we report that a CSF1R-CSF1 autocrine/paracrine signaling mechanism is constitutively activated in a subset of human OSA cases and is critical for promoting tumor growth and contributes to metastasis. Read More

Eur Radiol Exp 2020 Apr 3;4(1):22. Epub 2020 Apr 3.

Department of Translational Research, University of Pisa, Chair Radiodiagnostica 3, Pisa University Hospital, Via Roma 67, 56126, Pisa, Italy.

PRIMAGE is one of the largest and more ambitious research projects dealing with medical imaging, artificial intelligence and cancer treatment in children. It is a 4-year European Commission-financed project that has 16 European partners in the consortium, including the European Society for Paediatric Oncology, two imaging biobanks, and three prominent European paediatric oncology units. The project is constructed as an observational in silico study involving high-quality anonymised datasets (imaging, clinical, molecular, and genetics) for the training and validation of machine learning and multiscale algorithms. Read More

J Hepatol 2020 Mar 30. Epub 2020 Mar 30.

Childhood Liver Oncology Group, Germans Trias i Pujol Research Institute (IGTP), Program for Predictive and Personalized Medicine of Cancer (PMPPC), Badalona, Spain; CIBER, Hepatic and Digestive Diseases, Barcelona, Spain. Electronic address:

Background And Aims: Hepatoblastoma (HB) is a rare disease. Nevertheless, it is the predominant pediatric liver cancer, with limited therapeutic options for patients with aggressive tumors. Here we sought to increase knowledge of HB pathobiology in an effort to move towards precision medicine. Read More

Nucleic Acid Ther 2020 Apr 2. Epub 2020 Apr 2.

Genetics and Genomic Medicine Department, UCL Great Ormond Street Institute of Child Health, London, United Kingdom.

Neuroblastoma (NB) is the most common solid tumor in childhood. Twenty percent of patients display amplification, which indicates a very poor prognosis. is a highly specific target for an NB tumor therapy as expression is absent or very low in most normal cells, while, as a transcription factor, it regulates many essential cell activities in tumor cells. Read More

Cancer Discov 2020 Apr 1. Epub 2020 Apr 1.

Division of Cancer Therapeutics and Department of Molecular Pathology, Institute of Cancer Research

Infant high grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histological review, methylation profiling, custom panel and genome/exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an 'intrinsic' spectrum of disease specific to the infant population. Read More

Chronobiol Int 2020 Apr 1:1-14. Epub 2020 Apr 1.

Institute and Policlinic for Occupational Medicine, Environmental Medicine and Prevention Research, University Hospital of Cologne, Cologne, Germany.

Experimental evidence suggests that perinatal light imprinting of circadian clocks and systems may affect downstream physiology and cancer risk in later life. For humans, the predominant circadian stimulus is the daily light-dark cycle. Herein, we explore associations between perinatal photoperiod characteristics (photoperiod: duration of daylight as determined by time-of-year and location) and childhood cancer risk. Read More

J Pathol Clin Res 2020 Mar 28. Epub 2020 Mar 28.

Department of Human Genetics, McGill University, Montréal, Canada.

Individuals with DICER1 syndrome, a genetic disorder caused by pathogenic germline variants in DICER1, are at increased risk of developing a wide array of predominantly childhood onset conditions, including genitourinary sarcomas. However, data on DICER1 involvement in paratesticular sarcomas have not been published. Herein, we analyse a series of 15 paediatric paratesticular sarcomas and describe in detail the case of a male infant with a paratesticular myxoid tumour, considered to be a low-grade sarcoma, who also manifested a cystic nephroma, a classic DICER1 syndrome phenotype. Read More

Am J Hum Genet 2020 04 19;106(4):570-583. Epub 2020 Mar 19.

Department of Pediatrics, Baylor College of Medicine (BCM), Houston, TX 77030, USA; Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Division of Neurology and Developmental Neuroscience, Department of Pediatrics, BCM, Houston, TX 77030, USA; Department of Molecular and Human Genetics, BCM, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA; Program in Development, Disease Models, and Therapeutics, BCM, Houston, TX 77030, USA; Department of Neuroscience, BCM, Houston, TX 77030, USA; McNair Medical Institute, The Robert and Janice McNair Foundation, Houston, TX 77030, USA. Electronic address:

EIF2AK1 and EIF2AK2 encode members of the eukaryotic translation initiation factor 2 alpha kinase (EIF2AK) family that inhibits protein synthesis in response to physiologic stress conditions. EIF2AK2 is also involved in innate immune response and the regulation of signal transduction, apoptosis, cell proliferation, and differentiation. Despite these findings, human disorders associated with deleterious variants in EIF2AK1 and EIF2AK2 have not been reported. Read More

Genes Chromosomes Cancer 2020 Jul 26;59(7):422-427. Epub 2020 Mar 26.

Division of Laboratory Genetics and Genomics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.

Infant leukemias are a rare group of neoplasms that are clinically and biologically distinct from their pediatric and adult counterparts. Unlike leukemia in older children where survival rates are generally favorable, infants with leukemia have a 5-year event-free survival rate of <50%. The majority of infant leukemias are characterized by KMT2A (MLL) rearrangements (~70 to 80% in acute lymphoblastic leukemia), which appear to be drivers of early leukemogenesis. Read More

J Cancer Res Clin Oncol 2020 May 18;146(5):1153-1167. Epub 2020 Mar 18.

Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, LMU Munich, Lindwurmstr. 2a, 80337, Munich, Germany.

Background: Hepatoblastoma (HB) and pediatric hepatocellular carcinoma (HCC) are the most common malignant liver tumors in childhood. Both tumor types exhibit genetic and epigenetic alterations in the WNT/β-catenin signaling pathway, which is a key regulator of liver progenitor cells in embryonic development. The tumors demonstrate a high rate of β-catenin mutations and gene expression changes of several WNT antagonists. Read More

Magy Onkol 2020 Mar 27;64(1):38-42. Epub 2020 Feb 27.

Orvosi Genetikai Intézet, PTE KK, Pécs, Hungary.

In the past few years there is an emerging need for clinical genetics counseling in the case of malignant diseases as well. For these reasons a novel professional recommendation has been developed for oncogenetic counseling, whose publication is in progress. In nearly 10% of childhood cancers there is an underlying tumor predisposition syndrome, but this value is thought to be underestimated. Read More

Acta Oncol 2020 Mar 14:1-10. Epub 2020 Mar 14.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

High birthweight may predispose children to acute lymphoid leukemia, whereas low birthweight is associated with childhood morbidity and mortality. Low and high birthweight have been inconsistently associated with mortality in children with leukemia. In a cohort of childhood and adolescent leukemia (0-19 years) patients from registries in Denmark, Norway, Sweden, and Washington State in the United States (1967-2015), five-year all-cause mortality was assessed by birthweight and other measures of fetal growth using the cumulative incidence function and Cox regression with adjustment for sex, diagnosis year, country, the presence of Down's syndrome or other malformations, and type of leukemia. Read More

Cancer Epidemiol Biomarkers Prev 2020 Mar 13. Epub 2020 Mar 13.

Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer, Vancouver, British Columbia, Canada.

Background: Familial aggregation of lymphoid cancers and immune-related disorders suggests a role for genetic susceptibility; however, few studies examine environmental factors. According to the hygiene hypothesis, adult-onset immune-related diseases may be a consequence of reduced childhood infectious exposures and aberrant immune development. In a cohort of 196 multiple-case lymphoid cancer families, we analyzed environmental factors related to the hygiene hypothesis. Read More

Hum Reprod Update 2020 Apr;26(3):368-391

Biology of the Testis, Research Laboratory for Reproduction, Genetics and Regenerative Medicine, Vrije Universiteit Brussel (VUB), 1090 Brussels, Belgium.

Background: Although the prognosis of childhood cancer survivors has increased dramatically during recent years, chemotherapy and radiation treatments for cancer and other conditions may lead to permanent infertility in prepubertal boys. Recent developments have shown that spermatogonial stem cell (SSC) transplantation may be a hope for restoring fertility in adult survivors of childhood cancers. For this reason, several centres around the world are collecting and cryopreserving testicular tissue or cells anticipating that, in the near future, some patients will return for SSC transplantation. Read More

Nat Commun 2020 Mar 11;11(1):1310. Epub 2020 Mar 11.

Oncode Institute, Princess Máxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS, Utrecht, The Netherlands.

Kidney tumours are among the most common solid tumours in children, comprising distinct subtypes differing in many aspects, including cell-of-origin, genetics, and pathology. Pre-clinical cell models capturing the disease heterogeneity are currently lacking. Here, we describe the first paediatric cancer organoid biobank. Read More

Ann Hum Biol 2020 Mar 9;47(2):173-180. Epub 2020 Mar 9.

Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, The Capital Region, Copenhagen, Denmark.

Body size in adult life is likely associated with risks of endometriosis and adenomyosis, yet little is known about associations with body size earlier in life. To examine whether birth weight, childhood body mass index (BMI) and height are associated with risks of endometriosis and adenomyosis. From the Copenhagen School Health Records Register, 171,447 girls born 1930-1996, with measured weights and heights at ages 7-13 were included. Read More

Blood Adv 2020 Mar;4(5):930-942

Murdoch Children's Research Institute, Parkville, VIC, Australia.

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, and implementation of risk-adapted therapy has been instrumental in the dramatic improvements in clinical outcomes. A key to risk-adapted therapies includes the identification of genomic features of individual tumors, including chromosome number (for hyper- and hypodiploidy) and gene fusions, notably ETV6-RUNX1, TCF3-PBX1, and BCR-ABL1 in B-cell ALL (B-ALL). RNA-sequencing (RNA-seq) of large ALL cohorts has expanded the number of recurrent gene fusions recognized as drivers in ALL, and identification of these new entities will contribute to refining ALL risk stratification. Read More

Am J Med Genet A 2020 May 6;182(5):1273-1277. Epub 2020 Mar 6.

Genetics and Molecular Pathology Research Laboratory, Centre for Cancer Biology, An Alliance Between SA Pathology and the University of South Australia, Adelaide, South Australia, Australia.

Autosomal dominant (de novo) mutations in PBX1 are known to cause congenital abnormalities of the kidney and urinary tract (CAKUT), with or without extra-renal abnormalities. Using trio exome sequencing, we identified a PBX1 p.(Arg107Trp) mutation in a deceased one-day-old neonate presenting with CAKUT, asplenia, and severe bilateral diaphragmatic thinning and eventration. Read More

J Pediatr Hematol Oncol 2020 Mar 3. Epub 2020 Mar 3.

Clinical Medicine Post-Graduation Program, Faculty of Medicine.

KMT2A gene rearrangements represent the most frequent group of abnormalities in childhood leukemia (~70% of cases), with over 120 rearrangements described. The investigation of KMT2A rearrangements is still a vast field to be explored. Several studies have been characterizing different outcomes and leukemogenic mechanisms, depending on the translocation partner gene involved in childhood KMT2A-r leukemias. Read More

Clin Cancer Res 2020 Mar 3. Epub 2020 Mar 3.

Division of Oncology, Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

The adoptive transfer of genetically engineered chimeric antigen receptor (CAR) T cells has opened a new frontier in cancer therapy. Unlike the paradigm of targeted therapies, the efficacy of CAR T-cell therapy depends not only on the choice of target but also on a complex interplay of tumor, immune, and stromal cell communication. This presents both challenges and opportunities from a discovery standpoint. Read More

Pediatr Blood Cancer 2020 May 2;67(5):e28231. Epub 2020 Mar 2.

Division of Hematology/Oncology, Hematology/Oncology Flow Cytometry Laboratory, Children's Hospital of Michigan, Detroit, Michigan.

Background: Proliferation of large granular lymphocytes (LGL) and T-cell LGL (T-LGL) in peripheral blood along with demonstration of clonality are the hallmarks of a heterogeneous group of disorders, including T-LGL leukemia or T-LGL lymphocytosis. They are often associated with neutropenia and responsive to immunosuppression. The true nature of this entity is not well understood. Read More