Search Our Scientific Publications & Authors

Am J Hum Genet 2019 Feb 11. Epub 2019 Feb 11.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital, Houston, TX 77030, USA. Electronic address:

SPONASTRIME dysplasia is an autosomal-recessive spondyloepimetaphyseal dysplasia characterized by spine (spondylar) abnormalities, midface hypoplasia with a depressed nasal bridge, metaphyseal striations, and disproportionate short stature. Scoliosis, coxa vara, childhood cataracts, short dental roots, and hypogammaglobulinemia have also been reported in this disorder. Although an autosomal-recessive inheritance pattern has been hypothesized, pathogenic variants in a specific gene have not been discovered in individuals with SPONASTRIME dysplasia. Read More

J Expo Sci Environ Epidemiol 2019 Feb 15. Epub 2019 Feb 15.

Department of Epidemiology, Human Genetics and Environmental Sciences, Southwest Center for Occupational and Environmental Health, The University of Texas Health Science Center at Houston (UTHealth) School of Public Health, 1200 Pressler Street, Houston, TX, 77030, USA.

Epidemiology studies relying on one address to assign exposures over time share common methodological limitations in failing to account for mobility that may introduce potential exposure misclassification. Using Texas birth certificate and cancer registry data, we identified predictors of residential mobility among mothers of children diagnosed with early childhood leukemia in Texas from 1995 to 2011. We used U. Read More

Int J Radiat Oncol Biol Phys 2019 Feb 12. Epub 2019 Feb 12.

Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA.

Background: The association of hyperthyroidism with exposure to ionizing radiation is poorly understood. This study addresses the risk of hyperthyroidism in relation to incidental therapeutic radiation dose to the thyroid and pituitary glands in a large cohort of survivors of childhood cancer.

Methods: Utilizing the Childhood Cancer Survivor Study, a cohort of five-year survivors of childhood cancer diagnosed at hospitals in the United States and Canada between 1970 and 1986, the occurrence of hyperthyroidism through 2009 was ascertained among 12,183 survivors based on serial questionnaires. Read More

Nat Rev Dis Primers 2019 Feb 14;5(1):11. Epub 2019 Feb 14.

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

Medulloblastoma (MB) comprises a biologically heterogeneous group of embryonal tumours of the cerebellum. Four subgroups of MB have been described (WNT, sonic hedgehog (SHH), Group 3 and Group 4), each of which is associated with different genetic alterations, age at onset and prognosis. These subgroups have broadly been incorporated into the WHO classification of central nervous system tumours but still need to be accounted for to appropriately tailor disease risk to therapy intensity and to target therapy to disease biology. Read More

Cancer 2019 Feb 13. Epub 2019 Feb 13.

Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden.

Background: Experimental models have demonstrated that immune surveillance by cytotoxic lymphocytes can protect from spontaneous neoplasms and cancer. In humans, defective lymphocyte cytotoxicity is associated with the development of hemophagocytic lymphohistiocytosis, a hyperinflammatory syndrome. However, to the best of the authors' knowledge, the degree to which human lymphocyte cytotoxicity protects from cancer remains unclear. Read More

Sci Rep 2019 Feb 12;9(1):1875. Epub 2019 Feb 12.

Department of Pediatric Oncology, Erasmus Medical Center - Sophia Children's Hospital, Rotterdam, The Netherlands.

The FGF receptor signaling pathway is recurrently involved in the leukemogenic processes. Oncogenic fusions of FGFR1 with various fusion partners were described in myeloid proliferative neoplasms, and overexpression and mutations of FGFR3 are common in multiple myeloma. In addition, fibroblast growth factors are abundant in the bone marrow, and they were shown to enhance the survival of acute myeloid leukemia cells. Read More

Br J Cancer 2019 Feb 12;120(4):435-443. Epub 2019 Feb 12.

Department of Breast cancer, Endocrine tumors and Sarcoma, Karolinska University Hospital, Stockholm, Sweden.

Background: Heterogeneity and low incidence comprise the biggest challenge in sarcoma diagnosis and treatment. Chemotherapy, although efficient for some sarcoma subtypes, generally results in poor clinical responses and is mostly recommended for advanced disease. Specific genomic aberrations have been identified in some sarcoma subtypes but few of them can be targeted with approved drugs. Read More

Int J Cancer 2019 Feb 6. Epub 2019 Feb 6.

Institute of Biomedicine, University of Turku, Turku, Finland.

Neurofibromatosis type 1 (NF1) is a cancer predisposition syndrome with an incidence of 1:2,000. Patients with NF1 have an increased cancer risk and mortality, but there are no population-based cohort studies specifically investigating the risk of childhood malignancies. We used the Finnish NF1 cohort to analyze the incidence, risk and prognosis of malignancies in NF1 patients <20 years of age. Read More

Am J Med Genet A 2019 Feb 4. Epub 2019 Feb 4.

Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Sotos syndrome is an overgrowth syndrome characterized by distinctive facial features and intellectual disability caused by haploinsufficiency of the NSD1 gene. Genotype-phenotype correlations have been observed, with major anomalies seen more frequently in patients with 5q35 deletions than those with point mutations in NSD1. Though endocrine features have rarely been described, transient hyperinsulinemic hypoglycemia (HI) of the neonatal period has been reported as an uncommon presentation of Sotos syndrome. Read More

Am J Med Genet A 2019 Feb 4. Epub 2019 Feb 4.

Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Beckwith-Wiedemann syndrome (BWS) is the most common epigenetic overgrowth disorder and presents with patients affected by a variety of clinical features. Although genotype-phenotype correlations have been demonstrated in BWS and although BWS has been reported to occur equally among racial and ethnic backgrounds, no study to date has evaluated the frequency of findings in different backgrounds. In this study, we evaluated the incidence of clinical features and molecular diagnoses among patients with BWS in Caucasian, Mixed, and non-Caucasian groups. Read More

Br J Haematol 2019 Feb 3. Epub 2019 Feb 3.

Department of Paediatric Oncology/Haematology, Charité Universitätsmedizin Berlin, Berlin, Germany.

Aneuploidy is common in paediatric B-cell precursor acute lymphoblastic leukaemia (ALL). Specific subgroups, such as high hyperdiploidy (>50 chromosomes or DNA Index ≥1·16) and hypodiploidy (<45 chromosomes), predict outcome of patients after primary treatment. Whether aneuploidy has a prognostic value for relapsed disease is yet to be determined. Read More

Clin Transl Oncol 2019 Feb 2. Epub 2019 Feb 2.

Descriptive Epidemiology, Genetics and Cancer Prevention Group, Biomedical Research Institute (IDIBGI), Girona, Spain.

Introduction: Pediatric central nervous system tumors are one of the most frequent types of neoplasms in children but epidemiological data on these tumors have been sparsely reported in the medical literature.

Materials And Methods: We analyze the epidemiology of this type of tumors performing a retrospective population-based study in pediatrics and adolescent age in the population of Girona and compare them with series from Spain, Europe and worldwide. Cases were registered using the International Classification of Disease for Oncology, third edition and grouping according the International Classification of Childhood Cancer, third edition (ICCC-3). Read More

Bone 2019 Jan 31;121:221-226. Epub 2019 Jan 31.

Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America; Department of Genetics, University of Pennsylvania, Philadelphia, PA, United States of America; Center for Spatial and Functional Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, United States of America. Electronic address:

Over the past two decades, a low frequency variant (rs1800012) within the first intron of the type I collagen alpha 1 (COLIA1) gene has been implicated in lower areal BMD (aBMD) and increased risk of osteoporotic fracture. This association is particularly strong in postmenopausal women, in whom net bone loss arises in the context of high bone turnover. High bone turnover also accompanies childhood linear growth; however, the role of rs1800012 in this stage of net bone accretion is less well understood. Read More

Cold Spring Harb Mol Case Stud 2019 Feb 1;5(1). Epub 2019 Feb 1.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas 77005, USA.

Li-Fraumeni syndrome (LFS) is an autosomal dominant condition associated with a high risk of a broad range of childhood- and adult-onset cancers. LFS is related to germline mutations of the tumor-suppressor gene The most common reported leukemia associated with LFS is hypodiploid acute lymphoblastic leukemia, but myeloid malignancies including acute myeloid leukemia (AML), chronic myeloid leukemia, and myelodysplastic syndrome (MDS) are also reported, often in the setting of therapy-related disease. We reviewed the clinicopathologic characteristics including cytogenetics and molecular analysis for seven adult patients with LFS and hematologic malignancies evaluated at the Hereditary Hematologic Malignancy Clinic (HHMC) at MD Anderson Cancer Center. Read More

EMBO Rep 2019 Jan 21. Epub 2019 Jan 21.

Biomedical Research Foundation Academy of Athens, Athens, Greece

Genome-wide studies in tumor cells have indicated that chromatin-modifying proteins are commonly mutated in human cancers. The lysine-specific methyltransferase 2C (KMT2C/MLL3) is a putative tumor suppressor in several epithelia and in myeloid cells. Here, we show that downregulation of KMT2C in bladder cancer cells leads to extensive changes in the epigenetic status and the expression of DNA damage response and DNA repair genes. Read More

Nat Commun 2019 01 21;10(1):419. Epub 2019 Jan 21.

Division of Genetics and Epidemiology, The Institute of Cancer Research, Sutton, Surrey, SM2 5NG, UK.

The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article. Furthermore, in the original HTML version of this Article, the order of authors within the author list was incorrect. Read More

Crit Rev Oncol Hematol 2019 Jan 3;133:129-141. Epub 2018 Nov 3.

Princess Máxima Centre for Pediatric Oncology, Utrecht, the Netherlands.

Over the past decades, survival rates of childhood cancer have increased considerably from 5 to 30% in the early seventies to current rates exceeding 80%. This is due to the development of effective chemotherapy, surgery, radiotherapy and stem cell transplantation, combined with an optimized stratification of therapy and better supportive care regimens. As a consequence, active surveillance strategies of late sequelae have been developed to improve the quality of survival. Read More

Int J Infect Dis 2019 Jan 17. Epub 2019 Jan 17.

University of Texas Health Science Center, School of Public Health, Department of Epidemiology, Human Genetics, and Environmental Sciences, Center for Infectious Diseases, Houston, Texas, USA; MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Microbiology and Infectious Diseases Program, Houston, Texas, USA. Electronic address:

Background: Diarrhea causes significant morbidity and mortality among children worldwide. Regions most affected by diarrhea are the sub-Saharan African and Southeast Asia, where antibiotics are in common use and can make children more vulnerable to Clostridium difficile and pathogens which are not affected by these drugs. Indeed, Clostridium difficile is a major diarrhea-associated pathogen and poses a significant threat to vulnerable and immunocompromised populations. Read More

Blood Adv 2019 Jan;3(2):148-157

Wolfson Childhood Cancer Research Centre, Northern Institute for Cancer Research, Newcastle University, Newcastle, United Kingdom.

Genetic abnormalities provide vital diagnostic and prognostic information in pediatric acute lymphoblastic leukemia (ALL) and are increasingly used to assign patients to risk groups. We recently proposed a novel classifier based on the copy-number alteration (CNA) profile of the 8 most commonly deleted genes in B-cell precursor ALL. This classifier defined 3 CNA subgroups in consecutive UK trials and was able to discriminate patients with intermediate-risk cytogenetics. Read More

J Biol Chem 2019 Jan 14. Epub 2019 Jan 14.

Children's Hospital Los Angeles and University of Southern California, United States.

Retinoblastoma is a childhood retinal tumor that develops from cone photoreceptor precursors in response to inactivating RB1 mutations and loss of functional RB protein. The cone precursor's response to RB loss involves cell-type-specific signaling circuitry that helps to drive tumorigenesis. One component of the cone precursor circuitry, the thyroid hormone receptor β2 (TRβ2), enables the aberrant proliferation of diverse RB-deficient cells in part by opposing the down-regulation of S-phase kinase-associated protein (SKP2) by the more widely expressed and tumor suppressive TRβ1. Read More

Leukemia 2019 Jan 11. Epub 2019 Jan 11.

Department of Biomedicine, School of Medicine, Josep Carreras Leukemia Research Institute, University of Barcelona, Barcelona, Spain.

B cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer, with cure rates of ∼80%. MLL-rearranged (MLLr) B-ALL (MLLr-B-ALL) has, however, an unfavorable prognosis with common therapy refractoriness and early relapse, and therefore new therapeutic targets are needed for relapsed/refractory MLLr-B-ALL. MLLr leukemias are characterized by the specific expression of chondroitin sulfate proteoglycan-4, also known as neuron-glial antigen-2 (NG2). Read More

Annu Rev Public Health 2019 Jan 11. Epub 2019 Jan 11.

Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden.

Mobile phones (MPs) are the most relevant source of radiofrequency electromagnetic field (RF-EMF) exposure to the brain and the salivary gland. Whether this exposure implies a cancer risk has been addressed in several case-control and few cohort studies. A meta-analysis of these studies does not show increased risks for meningioma, pituitary, and salivary gland tumors. Read More

J Psychosoc Oncol 2019 Jan 11:1-16. Epub 2019 Jan 11.

a Department of Ophthalmology & Vision Sciences , The Hospital for Sick Children , Toronto , Canada.

Objective: To characterize coping and distress among parents of children with retinoblastoma, and to uncover their association with perceived health literacy, self-efficacy, and social support.

Methods: This was a cross-sectional study performed in the retinoblastoma clinics of Beijing Children's Hospital, Jilin Eye Hospital and Changchun Hospital in China. Parents of children with retinoblastoma (n = 104) completed a print Mandarin language questionnaire consisting of four sections: (i) demographic information, (ii) mini-mental adjustment to cancer scale, (iii) hospital anxiety and depression scale, and (iv) perceived health literacy, self-efficacy, and social support scales. Read More

Oncotarget 2018 Dec 7;9(96):36878-36888. Epub 2018 Dec 7.

The Children's Guild Foundation Down Syndrome Research Program, Genetics and Genomics Program, Department of Cancer Genetics and Genomics, Roswell Park Cancer Institute, Buffalo, NY, USA.

Synovial sarcoma is the most common pediatric non-rhabdomyosarcoma soft tissue sarcoma and accounts for about 8-10% of all soft tissue sarcoma in childhood and adolescence. The presence of a chromosomal translocation-associated -fusion gene is causally linked to development of primary synovial sarcoma. Metastases occur in approximately 50-70% of synovial sarcoma cases with yet unknown mechanisms, which led to about 70-80% mortality rate in five years. Read More

Neuro Oncol 2019 Jan 6. Epub 2019 Jan 6.

Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida.

Background: Neurofibromatosis type 2 (NF2) is a genetic tumor-predisposition disorder caused by NF2/merlin tumor suppressor gene inactivation. The hallmark of NF2 is formation of bilateral vestibular schwannomas (VS). Because merlin modulates activity of the Ras/Raf/MEK/ERK pathway, we investigated repurposing drugs targeting MEK1/2 as a treatment for NF2-associated schwannomas. Read More

Hum Mol Genet 2019 Jan 7. Epub 2019 Jan 7.

Division of Genetics and Epidemiology.

Acta Oncol 2019 Jan 6:1-9. Epub 2019 Jan 6.

a School of Women's and Children's Health, UNSW , Sydney , Australia.

Introduction: Understanding the cause of their cancer is important for many cancer patients. Childhood cancer survivors'/survivors' parents' beliefs about cancer etiology are understudied. We aimed to assess survivors'/parents' beliefs about what causes childhood cancer, compared with beliefs in the community. Read More

Oncotarget 2018 Nov 30;9(94):36719. Epub 2018 Nov 30.

Division of Genetics & Epidemiology, Institute of Cancer Research, Sutton, UK.

[This corrects the article DOI: 10.18632/oncotarget.385. Read More

Am J Hum Genet 2019 Jan;104(1):76-93

Harvard Medical School, Boston, MA 02115, USA; Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA. Electronic address:

Genomic sequencing provides many opportunities in newborn clinical care, but the challenges of interpreting and reporting newborn genomic sequencing (nGS) results need to be addressed for its broader and effective application. The BabySeq Project is a pilot randomized clinical trial that explores the medical, behavioral, and economic impacts of nGS in well newborns and those admitted to a neonatal intensive care unit (NICU). Here we present childhood-onset and actionable adult-onset disease risk, carrier status, and pharmacogenomics findings from nGS of 159 newborns in the BabySeq Project. Read More

J Child Neurol 2019 Jan 4:883073818821036. Epub 2019 Jan 4.

2 Genetic Counseling Program, University of Texas MD Anderson Cancer Center, UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA.

Identifying genetic diagnoses for neurologic conditions with a considerable hereditary component, such as autism spectrum disorder, intellectual disability, and epilepsy, is critical to providing proper medical management for patients and their families. However, many patients with these conditions are not tested appropriately or receive no genetic testing at all. The current study was designed to characterize the genetic testing practices of the providers most likely to evaluate or order genetic testing for these patients: pediatric neurologists, geneticists, and genetic counselors. Read More

Nature 2019 01 2;565(7739):312-317. Epub 2019 Jan 2.

Department of Pathology and Tumor Biology, Kyoto University, Kyoto, Japan.

Clonal expansion in aged normal tissues has been implicated in the development of cancer. However, the chronology and risk dependence of the expansion are poorly understood. Here we intensively sequence 682 micro-scale oesophageal samples and show, in physiologically normal oesophageal epithelia, the progressive age-related expansion of clones that carry mutations in driver genes (predominantly NOTCH1), which is substantially accelerated by alcohol consumption and by smoking. Read More

J Res Med Sci 2018 28;23:101. Epub 2018 Nov 28.

Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Cancer is the second most common cause of morbidity and mortality in children. This study aimed to epidemiologically and demographically assess common cancers in children in Iran.

Materials And Methods: This cohort study was conducted on children registered in Mahak Hospital and Rehabilitation Complex (which is a non-governmental organizations (NGO)-related hospital for only malignant diseases). Read More

Cancer Cell 2019 Jan 27;35(1):140-155.e7. Epub 2018 Dec 27.

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address:

Diffuse intrinsic pontine gliomas (DIPGs) are incurable childhood brainstem tumors with frequent histone H3 K27M mutations and recurrent alterations in PDGFRA and TP53. We generated genetically engineered inducible mice and showed that H3.3 K27M enhanced neural stem cell self-renewal while preserving regional identity. Read More

Cancer Cell 2019 Jan 27;35(1):95-110.e8. Epub 2018 Dec 27.

Hopp-Children's Cancer Center at the NCT Heidelberg (KiTZ), 69120 Heidelberg, Germany; Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Electronic address:

Biallelic inactivation of SMARCB1, encoding a member of the SWI/SNF chromatin remodeling complex, is the hallmark genetic aberration of atypical teratoid rhabdoid tumors (ATRT). Here, we report how loss of SMARCB1 affects the epigenome in these tumors. Using chromatin immunoprecipitation sequencing (ChIP-seq) on primary tumors for a series of active and repressive histone marks, we identified the chromatin states differentially represented in ATRTs compared with other brain tumors and non-neoplastic brain. Read More

Anticancer Res 2019 Jan;39(1):173-175

Stem Cell Laboratory, Center for Bone Marrow Transplants, Brazilian National Cancer Institute - INCA, Rio de Janeiro, Brazil.

Background/aim: Although the knowledge regarding adrenocortical carcinomas (ACC) tumorigenesis has significantly improved during the last decade, it still remains to be completely determined. Epithelial-mesenchymal transition (EMT) is a well described transcription factor induced process, postulated as an essential step toward cancer progression and metastasis development. In this context, Twist1 has been described as the EMT master-regulator. Read More

Crit Rev Toxicol 2018 Oct 27;48(9):789-795. Epub 2018 Dec 27.

a CAPHRI Research Institute and Department of Complex Genetics , Maastricht University , Maastricht , The Netherlands.

The incidence rates of a wide range of diseases and conditions have increased over the last decades. There is controversy over the origin of these increases, whether they are caused by exposure to compounds thought to have an effect on the endocrine system, the "endocrine disruption theory", or whether some other factor is responsible. In this analysis, the authors take a closer look at the role that changes in reproductive factors have played in this respect. Read More

EBioMedicine 2019 Jan 20;39:358-368. Epub 2018 Dec 20.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Background: Endemic Burkitt lymphoma (eBL) is an aggressive childhood B-cell lymphoma linked to Plasmodium falciparum (Pf) malaria in sub-Saharan Africa. We investigated antibody reactivity to several human receptor-binding domains of the Pf erythrocyte membrane protein 1 (PfEMP1) that play a key role in malaria pathogenesis and are targets of acquired immunity to malaria.

Methods: Serum/plasma IgG antibody reactivity was measured to 22 Pf antigens, including 18 to PfEMP1 CIDR domains between cases and controls from two populations (149 eBL cases and 150 controls from Ghana and 194 eBL cases and 600 controls from Uganda). Read More

Leukemia 2018 Dec 19. Epub 2018 Dec 19.

Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands.

Variation in survival of pediatric acute myeloid leukemia (pAML) over time and between Western European countries exists. The aim of the current study is to assess the progress made for the Dutch pAML population (0-17 years) during 1990-2015, based on trends in incidence, survival and mortality. Data from the population-based Netherlands Cancer Registry were merged with leukemia-related characteristics and treatment specifics from the Dutch Childhood Leukemia Study Group (Dutch Childhood Oncology Group (DCOG) from 2002 onwards). Read More

Int J Cancer 2018 Nov 22. Epub 2018 Nov 22.

Laboratory of Pathology, National Cancer Institute, Bethesda, MD.

Our previous study of DNA methylation in the pediatric soft tissue tumor rhabdomyosarcoma (RMS) demonstrated that fusion-positive (FP) and fusion-negative (FN) RMS tumors exhibit distinct DNA methylation patterns. To further examine the significance of DNA methylation differences in RMS, we investigated genome-wide DNA methylation profiles in discovery and validation cohorts. Unsupervised analysis of DNA methylation data identified novel distinct subsets associated with the specific fusion subtype in FP RMS and with RAS mutation status in FN RMS. Read More

Head Neck 2018 Dec 15. Epub 2018 Dec 15.

Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston, MA, USA.

Background: Recommendations for perioperative therapy in head and neck cancer are not explicit and recurrence occurs frequently. Circulating tumor DNA is an emerging cancer biomarker, but has not been extensively explored for detection of recurrence in head and neck cancer.

Methods: Patients diagnosed with head and neck squamous cell carcinoma were recruited into the study protocol. Read More

mSphere 2018 12 12;3(6). Epub 2018 Dec 12.

Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland, USA.

Several immunodeficiencies are associated with high susceptibility to persistent and progressive human papillomavirus (HPV) infection leading to a wide range of cutaneous and mucosal lesions. However, the HPV types most commonly associated with such clinical manifestations in these patients have not been systematically defined. Here, we used virion enrichment, rolling circle amplification, and deep sequencing to identify circular DNA viruses present in skin swabs and/or wart biopsy samples from 48 patients with rare genetic immunodeficiencies, including patients with warts, hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome, or epidermodysplasia verruciformis (EV). Read More

Am J Epidemiol 2018 12 7. Epub 2018 Dec 7.

Division of Genetics and Epidemiology, The Institute of Cancer Research, London, United Kingdom.

A balanced Robertsonian translocation results from fusion of two acrocentric chromosomes. Carriers are phenotypically normal, and are often diagnosed because of recurrent miscarriages, infertility or aneuploid offspring. Mortality and site-specific cancer risks in carriers have not been prospectively investigated. Read More

J Vis Exp 2018 Nov 21(141). Epub 2018 Nov 21.

CLIP - Childhood Leukemia Investigation Prague, Second Faculty of Medicine, Laboratory of Molecular Genetics, Charles University, Prague;

The metabolic requirement of cancer cells can negatively influence survival and treatment efficacy. Nowadays, pharmaceutical targeting of metabolic pathways is tested in many types of tumors. Thus, characterization of cancer cell metabolic setup is inevitable in order to target the correct pathway to improve the overall outcome of patients. Read More

Clin Cancer Res 2018 Dec 7. Epub 2018 Dec 7.

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

Pilocytic astrocytoma is the most common childhood brain tumor, characterized by constitutive MAPK activation. MAPK signaling induces oncogene-induced senescence (OIS), which may cause unpredictable growth behavior of pilocytic astrocytomas. The senescence-associated secretory phenotype (SASP) has been shown to regulate OIS, but its role in pilocytic astrocytoma remains unknown. Read More

Mol Ther Oncolytics 2018 Dec 18;11:62-74. Epub 2018 Oct 18.

Center for Childhood Cancer and Blood Diseases, Nationwide Children's Hospital, The Ohio State University, Columbus, OH 43205, USA.

Ewing sarcoma is a highly aggressive cancer that promotes the infiltration and activation of pro-tumor M2-like macrophages. Oncolytic virotherapy that selectively infects and destroys cancer cells is a promising option for treating Ewing sarcoma. The effect of tumor macrophages on oncolytic virus therapy, however, is variable among solid tumors and is unknown in Ewing sarcoma. Read More

Hematology Am Soc Hematol Educ Program 2018 11;2018(1):286-300

Department of Pediatrics, Benioff Children's Hospital and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA.

Over the past decade, there has been exponential growth in the number of genome sequencing studies performed across a spectrum of human diseases as sequencing technologies and analytic pipelines improve and costs decline. Pediatric hematologic malignancies have been no exception, with a multitude of next generation sequencing studies conducted on large cohorts of patients in recent years. These efforts have defined the mutational landscape of a number of leukemia subtypes and also identified germ-line genetic variants biologically and clinically relevant to pediatric leukemias. Read More

Semin Hematol 2018 Oct 29;55(4):235-241. Epub 2018 May 29.

Division of Pediatric Hematology-Oncology, Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, Montreal, Quebec, Canada. Electronic address:

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is a recently identified high-risk subtype of B-lineage ALL (B-ALL), characterized by a gene expression profile similar to that of Philadelphia-positive (Ph+) ALL, but without the hallmark BCR-ABL1 oncoprotein. Ph-like ALL represents approximately 15% of childhood ALL and its frequency rises with age, peaking among adolescents, and young adults with B-ALL. This subtype is associated with adverse clinical features, persistence of minimal residual disease, and a poor prognosis despite modern chemotherapy regimens. Read More

Fam Cancer 2018 Nov 26. Epub 2018 Nov 26.

Department of Pathology, Duke University Medical Center, 199B-MSRB Building, Research Drive, DUMC-3156, Durham, NC, 27710, USA.

Precise genetic counseling and prenatal diagnosis are often hindered by incomplete penetrance of risk variance and complex patterns of inheritance. Here, we performed a clinical and genetic study of a five-generation Pakistani family with a history of multiple cases of childhood brain tumors. Six affected individuals died of brain tumors at very early ages and three were confirmed as having a homozygous mutation in exon 6 of the PMS2 gene (c. Read More

Oncogene 2018 Nov 26. Epub 2018 Nov 26.

Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

The poor outcomes in infant acute lymphoblastic leukemia (ALL) necessitate new treatments. Here we discover that EIF4E protein is elevated in most cases of infant ALL and test EIF4E targeting by the repurposed antiviral agent ribavirin, which has anticancer properties through EIF4E inhibition, as a potential treatment. We find that ribavirin treatment of actively dividing infant ALL cells on bone marrow stromal cells (BMSCs) at clinically achievable concentrations causes robust proliferation inhibition in proportion with EIF4E expression. Read More