73 results on '"WILMS-TUMOR"'
Search Results
2. Tumorprädispositionssyndrome und Nephroblastom: Frühe Diagnose mit Bildgebung.
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Welter, N., Furtwängler, R., Schneider, G., Graf, N., and Schenk, J.-P.
- Abstract
Copyright of Die Radiologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2022
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3. Solide Tumoren im Kindesalter.
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Fuchs, J., Warmann, S. W., and Eckoldt, F.
- Abstract
Copyright of Der Onkologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2021
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4. Seltene kindliche Nierentumoren.
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Vokuhl, C.
- Abstract
Copyright of Der Pathologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2019
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5. Embryonal rhabdomyosarcoma of the uterine corpus: a clinicopathological and molecular analysis of 21 cases highlighting a frequent association with DICER1 mutations
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Leanne de Kock, Esther Oliva, Andre Pinto, Robert H. Young, Zehra Ordulu, Jennifer A. Bennett, W. Glenn McCluggage, William D. Foulkes, Lauren L. Ritterhouse, Koen Van de Vijver, Rajeev Shah, Pankhuri Wanjari, and Eike Burandt
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Adult ,Ribonuclease III ,0301 basic medicine ,Neuroblastoma RAS viral oncogene homolog ,Pathology ,medicine.medical_specialty ,Tumor Cell Necrosis ,Pleuropulmonary blastoma ,medicine.disease_cause ,MULLERIAN ADENOSARCOMA ,Pathology and Forensic Medicine ,UTERUS ,DEAD-box RNA Helicases ,03 medical and health sciences ,0302 clinical medicine ,Medicine and Health Sciences ,medicine ,Humans ,Rhabdomyosarcoma, Embryonal ,HETEROLOGOUS ELEMENTS ,WILMS-TUMOR ,Anaplasia ,Aged ,DICER1 Syndrome ,business.industry ,PLEUROPULMONARY BLASTOMA ,PURE ALVEOLAR RHABDOMYOSARCOMA ,Wilms' tumor ,Middle Aged ,medicine.disease ,GENOMIC ANALYSIS ,030104 developmental biology ,030220 oncology & carcinogenesis ,Mutation ,Uterine Neoplasms ,CHILDHOOD RHABDOMYOSARCOMA ,Female ,Embryonal rhabdomyosarcoma ,KRAS ,medicine.symptom ,PRIMARY OVARIAN RHABDOMYOSARCOMA ,URINARY-BLADDER ,business - Abstract
Herein we evaluated a series of 21 embryonal rhabdomyosarcomas of the uterine corpus (ucERMS), a rare neoplasm, to characterize their morphology, genomics, and behavior. Patients ranged from 27 to 73 (median 52) years and tumors from 4 to 15 (median 9) cm, with extrauterine disease noted in two. Follow-up (median 16 months) was available for 14/21 patients; nine were alive and well, four died of disease, and one died from other causes. Most tumors (16/21) showed predominantly classic morphology, comprised of alternating hyper- and hypocellular areas of primitive small cells and differentiating rhabdomyoblasts in a loose myxoid/edematous stroma. A cambium layer was noted in all; seven had heterologous elements (six with fetal-type cartilage) and eight displayed focal anaplasia. The remaining five neoplasms showed only a minor component (
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- 2021
6. A Summary of the Inaugural WHO Classification of Pediatric Tumors: Transitioning from the Optical into the Molecular Era
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Stefan M. Pfister, Miguel Reyes-Múgica, John K.C. Chan, Henrik Hasle, Alexander J. Lazar, Sabrina Rossi, Andrea Ferrari, Jason A. Jarzembowski, Kathy Pritchard-Jones, D. Ashley Hill, Thomas S. Jacques, Pieter Wesseling, Dolores H. López Terrada, Andreas von Deimling, Christian P. Kratz, Ian A. Cree, and Rita Alaggio
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Brain Neoplasms ,CENTRAL-NERVOUS-SYSTEM ,WORKING GROUP ,Genomics ,World Health Organization ,BETA-CATENIN ,GENOMIC ANALYSIS ,SOFT-TISSUE SARCOMAS ,HIGH-RISK ,Oncology ,GENETIC ALTERATIONS ,YOUNG-ADULTS ,Humans ,Child ,WILMS-TUMOR ,METHYLATION-BASED CLASSIFICATION - Abstract
Pediatric tumors are uncommon, yet are the leading cause of cancer-related death in childhood. Tumor types, molecular characteristics, and pathogenesis are unique, often originating from a single genetic driver event. The specific diagnostic challenges of childhood tumors led to the development of the first World Health Organization (WHO) Classification of Pediatric Tumors. The classification is rooted in a multilayered approach, incorporating morphology, IHC, and molecular characteristics. The volume is organized according to organ sites and provides a single, state-of-the-art compendium of pediatric tumor types. A special emphasis was placed on “blastomas,” which variably recapitulate the morphologic maturation of organs from which they originate. Significance: In this review, we briefly summarize the main features and updates of each chapter of the inaugural WHO Classification of Pediatric Tumors, including its rapid transition from a mostly microscopic into a molecularly driven classification systematically taking recent discoveries in pediatric tumor genomics into account.
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- 2021
7. Nephroblastome.
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Bode, P. and Moch, H.
- Abstract
Copyright of Der Pathologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2016
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8. Genotyp-Phänotyp-Korrelation bei Nephropathien mit WT1-Mutation.
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Lemke, A., Müller-Wiefel, D., and Kemper, M.
- Abstract
Copyright of Der Nephrologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2015
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9. The Association Between High Birth Weight and Long-Term Outcomes—Implications for Assisted Reproductive Technologies : A Systematic Review and Meta-Analysis
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Magnusson, Åsa, Laivuori, Hannele, Loft, Anne, Oldereid, Nan B., Pinborg, Anja, Petzold, Max, Romundstad, Liv Bente, Söderström-Anttila, Viveca, Bergh, Christina, Tampere University, Department of Gynaecology and Obstetrics, Clinical Medicine, HUS Gynecology and Obstetrics, Genomics of Neurological and Neuropsychiatric Disorders, Institute for Molecular Medicine Finland, Pregnancy and Genes, Department of Medical and Clinical Genetics, Helsinki Institute of Life Science HiLIFE, Clinicum, and University of Helsinki
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diabetes ,PERINATAL RISK-FACTORS ,CENTRAL-NERVOUS-SYSTEM ,assisted reproduction ,BLOOD-PRESSURE ,large for gestational age ,DEPENDENT DIABETES-MELLITUS ,BREAST-CANCER RISK ,high birth weight ,long-term morbidity ,BODY-MASS INDEX ,3123 Gynaecology and paediatrics ,cancer ,CHILDHOOD LEUKEMIA ,frozen embryo transfer ,WILMS-TUMOR ,GESTATIONAL-AGE ,ACUTE LYMPHOBLASTIC-LEUKEMIA - Abstract
Background: Studies have shown that the prevalence of children born with high birth weight or large for gestational age (LGA) is increasing. This is true for spontaneous pregnancies; however, children born after frozen embryo transfer (FET) as part of assisted reproductive technology (ART) also have an elevated risk. In recent years, the practice of FET has increased rapidly and while the perinatal and obstetric risks are well-studied, less is known about the long-term health consequences. Objective: The aim of this systematic review was to describe the association between high birth weight and LGA on long-term child outcomes. Data Sources: PubMed, Scopus, and Web of Science were searched up to January 2021. Exposure included high birth weight and LGA. Long-term outcome variables included malignancies, psychiatric disorders, cardiovascular disease, and diabetes. Study Selection: Original studies published in English or Scandinavian languages were included. Studies with a control group were included while studies published as abstracts and case reports were excluded. Data Extraction: The methodological quality, in terms of risk of bias, was assessed by pairs of reviewers. Robins-I (www.methods.cochrane.org) was used for risk of bias assessment in original articles. For systematic reviews, AMSTAR (www.amstar.ca) was used. For certainty of evidence, we used the GRADE system. The systematic review followed PRISMA guidelines. When possible, meta-analyses were performed. Results: The search included 11,767 articles out of which 173 met the inclusion criteria and were included in the qualitative analysis, while 63 were included in quantitative synthesis (meta-analyses). High birth weight and/or LGA was associated with low to moderately elevated risks for certain malignancies in childhood, breast cancer, several psychiatric disorders, hypertension in childhood, and type 1 and 2 diabetes. Conclusions: Although the increased risks for adverse outcome in offspring associated with high birth weight and LGA represent serious health effects in childhood and in adulthood, the size of these effects seems moderate. The identified risk association should, however, be taken into account in decisions concerning fresh and frozen ART cycles and is of general importance in view of the increasing prevalence in high birthweight babies. publishedVersion
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- 2021
10. Lebervenenverschlußkrankheit (Venoocclusive Disease) — Vortäuschen eines akuten Abdomens bei der Chemotherapie von Wilms-Tumoren
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Tröbs, R. B., Rothe, K., Meier, T., Hartel, W., editor, and Pichlmayr, R.
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- 1996
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11. Genetik der kongenitalen Aniridie.
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Neuhaus, C., Betz, C., Bergmann, C., and Bolz, H.J.
- Abstract
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- Published
- 2014
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12. Spina bifida and pediatric cancers
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Onyebuchi A. Arah, Jørn Olsen, Julia E. Heck, Noah Federman, Pei-Chen Lee, Chung Yi Li, Johnni Hansen, Fei Yu, Chia Kai Wu, Di He, and Beate Ritz
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Denmark ,CHILDREN ,FOLIC-ACID ,Cardiorespiratory Medicine and Haematology ,CONGENITAL-ABNORMALITIES ,Central Nervous System Neoplasms ,0302 clinical medicine ,Risk Factors ,Neoplasms ,Odds Ratio ,Prevalence ,2.1 Biological and endogenous factors ,Registries ,Aetiology ,BRAIN ,Child ,Spinal Dysraphism ,Cancer ,Pediatric ,RISK ,education.field_of_study ,Obstetrics ,Rehabilitation ,Hematology ,ASSOCIATION ,spina bifida ,Oncology ,030220 oncology & carcinogenesis ,Child, Preschool ,medicine.medical_specialty ,congenital, hereditary, and neonatal diseases and abnormalities ,Adolescent ,Population ,Taiwan ,folate ,Article ,03 medical and health sciences ,Young Adult ,Rare Diseases ,medicine ,Humans ,Oncology & Carcinogenesis ,WILMS-TUMOR ,education ,Preschool ,central nervous system tumors ,Fetus ,Pregnancy ,childhood cancer epidemiology ,CHILDHOOD-CANCER ,Spina bifida ,business.industry ,Prevention ,Neurosciences ,Infant ,Odds ratio ,medicine.disease ,Pediatric cancer ,Confidence interval ,Brain Disorders ,Birth defects ,Pediatrics, Perinatology and Child Health ,business ,030215 immunology - Abstract
Spina bifida has been reported to co-occur with pediatric cancer, but comprehensive evaluations remained elusive. We investigated this co-occurrence in two large, population-based studies in Taiwan (N = 1900 cancer cases, 2,077,137 controls) and Denmark (N = 5508 cases, 137,700 controls). Analyses in Denmark were restricted to the period before prenatal diagnostics became available (2004) and pregnancy terminations of fetuses with birth defects became more common. Using national patient and cancer registries, we linked spina bifida and cancer diagnoses among cases and non-cases. The risk of spina bifida among all cancer cases was increased and similar in Denmark [odds ratio (OR)=8.4, 95% confidence interval (CI) 5.1-13.8] and Taiwan (OR = 8.5, 95% CI 4.0-17.8), particularly for central nervous system (CNS) tumors (Denmark: OR = 16.3, 95% CI 8.1-33.0; Taiwan: OR = 26.6, 95% CI 8.5, 83.1), including benign CNS tumors (Denmark: OR = 41.5, 95% CI 21.2, 81.4). These findings suggest the need for comprehensive investigation of shared risk factors in the link between spina bifida and pediatric cancer.
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- 2020
13. Genetische Prädisposition für Wilms-Tumor.
- Author
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Royer-Pokora, B.
- Abstract
Copyright of Medizinische Genetik is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2007
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14. Multizystischer Nierentumor bei einem Patienten mit WAGR-Syndrom.
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Braun, K.-P., May, M., Erler, T., and Hoschke, B.
- Abstract
Copyright of Der Urologe A is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2007
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15. Kongenitale urogenitale Fehlbildungen bei Nephroblastomen.
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Zugor, V., Krot, D., and Schott, G.E.
- Abstract
Copyright of Der Urologe A is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2007
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16. Wilms-Tumoren im Erwachsenenalter.
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Zugor, Vahudin, Krot, D., Kühn, R., Schrott, K.M., and Schott, G.E.
- Abstract
Copyright of Der Urologe A is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2007
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17. Risikofaktoren intra- und postoperativer Komplikationen in der Chirurgie des Wilms-Tumors.
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Zugor, Vahudin, Krot, D., and Schott, G.E.
- Abstract
Copyright of Der Urologe A is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2007
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18. Wilms-Tumor.
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Seseke, F., Gutjahr, P., and Kremens, B.
- Abstract
Copyright of Der Urologe A is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2006
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19. Nephroblastom — Wilms-Tumor.
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Furtwängler, R., Schenk, J.-P., Reinhard, H., Leuschner, I., Rübe, C., Schweinitz, D., and Graf, N.
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Copyright of Der Onkologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2005
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20. Denys-Drash-Syndrom.
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Zugor, V., Zenker, M., Dötsch, J., Schrott, K., and Schott, G.
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Copyright of Der Urologe A is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2005
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21. Die Prognose des Wilms-Tumors im Verlauf der SIOP-Studien.
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Graf, N., Semler, O., and Reinhard, H.
- Abstract
Copyright of Der Urologe A is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2004
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22. Trim37-deficient mice recapitulate several features of the multi-organ disorder Mulibrey nanism
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Anu Jalanko, Susann Karlberg, Niklas Karlberg, Matti Jauhiainen, J. Kalervo Hiltunen, Kirsi Sainio, Anna-Elina Lehesjoki, Riikka H. Hämäläinen, Teija T. Toivonen, Natalia Kulesskaya, Marita Lipsanen-Nyman, Vootele Voikar, Kaisa Kettunen, Jorma Toppari, Elina Ikonen, Hannu Jalanko, Maarit Hölttä-Vuori, Riitta Karikoski, Vasily D. Antonenkov, Institute for Molecular Medicine Finland, Neuroscience Center, Research Programme for Molecular Neurology, Research Programs Unit, Heikki Rauvala Research Group, Medicum, Department of Anatomy, Lipid Trafficking Lab, Department of Biochemistry and Developmental Biology, Clinicum, Children's Hospital, Endokrinologian yksikkö, Lastentautien yksikkö, Anna-Elina Lehesjoki / Principal Investigator, and HUS Children and Adolescents
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0301 basic medicine ,Mulibrey nanism ,medicine.medical_specialty ,COILED-COIL PROTEIN ,QH301-705.5 ,Cardiomyopathy ,Science ,LUTEINIZING-HORMONE ,BIOGENESIS ,Congenic ,Biology ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,FINGER PROTEIN TRIM37 ,0302 clinical medicine ,MOUSE MODELS ,Internal medicine ,Fatty liver ,medicine ,Biology (General) ,WILMS-TUMOR ,Testosterone ,ENZYME DEFICIENCIES ,Growth failure ,LIPID HOMEOSTASIS ,ta1184 ,3112 Neurosciences ,medicine.disease ,3. Good health ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Infertility ,3121 General medicine, internal medicine and other clinical medicine ,Tumorigenesis ,RAT ,3111 Biomedicine ,General Agricultural and Biological Sciences ,Carcinogenesis ,Luteinizing hormone ,PEROXISOMES ,030217 neurology & neurosurgery ,Germ cell ,Hormone ,Research Article - Abstract
Mulibrey nanism (MUL) is a rare autosomal recessive multi-organ disorder characterized by severe prenatal-onset growth failure, infertility, cardiopathy, risk for tumors, fatty liver, and type 2 diabetes. MUL is caused by loss-of-function mutations in TRIM37, which encodes an E3 ubiquitin ligase belonging to the tripartite motif (TRIM) protein family and having both peroxisomal and nuclear localization. We describe a congenic Trim37 knock-out mouse (Trim37−/−) model for MUL. Trim37−/− mice were viable and had normal weight development until approximately 12 months of age, after which they started to manifest increasing problems in wellbeing and weight loss. Assessment of skeletal parameters with computer tomography revealed significantly smaller skull size, but no difference in the lengths of long bones in Trim37−/− mice as compared with wild-type. Both male and female Trim37−/− mice were infertile, the gonads showing germ cell aplasia, hilus and Leydig cell hyperplasia and accumulation of lipids in and around Leydig cells. Male Trim37−/− mice had elevated levels of follicle-stimulating and luteinizing hormones, but maintained normal levels of testosterone. Six-month-old Trim37−/− mice had elevated fasting blood glucose and low fasting serum insulin levels. At 1.5 years Trim37−/− mice showed non-compaction cardiomyopathy, hepatomegaly, fatty liver and various tumors. The amount and morphology of liver peroxisomes seemed normal in Trim37−/− mice. The most consistently seen phenotypes in Trim37−/− mice were infertility and the associated hormonal findings, whereas there was more variability in the other phenotypes observed. Trim37−/− mice recapitulate several features of the human MUL disease and thus provide a good model to study disease pathogenesis related to TRIM37 deficiency, including infertility, non-alcoholic fatty liver disease, cardiomyopathy and tumorigenesis., Summary: A congenic Trim37-deficient mouse model recapitulates several features of the human disorder Mulibrey nanism, and thus provides a good model to study disease pathogenesis related to TRIM37 deficiency.
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- 2016
23. Nephroblastome: Praktisch immer in Studien!
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Bode, P. K. and Moch, H.
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- 2016
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24. Die prognostische Bedeutung eines genetischen Zugewinns auf Chromosom 1q bei Wilms-Tumor
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Harde, Wiebke, Röcken, Christoph, Naumann, Carsten Maik, Prof. Dr. med. Christoph Röcken, and Priv.-Doz. Dr. Carsten Maik Naumann
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doctoral thesis ,Abschlussarbeit ,Wilms-Tumor ,Medizinische Fakultät ,Chromosom 1q ,Prognose ,Wilms-Tumor, Prognose, Chromosom 1q, Genetik ,ddc:610 ,Genetik ,ddc:6XX ,Faculty of Medicine - Abstract
In der Arbeit wurden Wilms-Tumore mit hohem Risiko sowie als Vergleich alle neu aufgetretenen Tumore in Deutschland 2007 auf einen genetischen Zugewinn auf Chromosom 1q untersucht. Dies wurde mit dem Krankheitsverlauf korreliert, um zu prüfen, ob diese genetische Alteration als prognostischer Faktor genutzt werden kann.
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- 2018
25. Parental age and childhood cancer risk: A Danish population-based registry study
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Julia E. Heck, Zuelma A. Contreras, Jørn Olsen, Beate Ritz, Fei Yu, and Johnni Hansen
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Parents ,Male ,Cancer Research ,Pediatrics ,Lymphoma ,Epidemiology ,Denmark ,CHILDREN ,FERTILITY TREATMENTS ,0302 clinical medicine ,Risk Factors ,YOUNG-ADULTS ,Medicine and Health Sciences ,Medicine ,2.1 Biological and endogenous factors ,030212 general & internal medicine ,DOWN-SYNDROME ,Registries ,Aetiology ,Child ,Cancer ,Pediatric ,education.field_of_study ,Lymphoma, Non-Hodgkin ,Hematology ,Middle Aged ,Precursor Cell Lymphoblastic Leukemia-Lymphoma ,ADVANCED PATERNAL AGE ,Oncology ,Child, Preschool ,030220 oncology & carcinogenesis ,language ,Public Health and Health Services ,Female ,Childhood cancer ,Adult ,medicine.medical_specialty ,Pediatric Research Initiative ,Adolescent ,Offspring ,Childhood Leukemia ,Pediatric Cancer ,Population ,Oncology and Carcinogenesis ,Non-Hodgkin ,Wilms Tumor ,Article ,BIRTH CHARACTERISTICS ,Danish ,03 medical and health sciences ,Paternal age ,Rare Diseases ,Parental age ,ASSISTED REPRODUCTIVE TECHNOLOGY ,SPORADIC HEREDITARY RETINOBLASTOMA ,Humans ,ACUTE-LEUKEMIA ,Oncology & Carcinogenesis ,Risk factor ,WILMS-TUMOR ,education ,Preschool ,Maternal age ,business.industry ,Prevention ,Infant ,Odds ratio ,medicine.disease ,language.human_language ,Cancer registry ,Logistic Models ,Case-Control Studies ,business ,Demography - Abstract
Background: Though the association between parental age at child's birth and the risk of childhood cancer has been previously investigated, the evidence to date is inconclusive and scarce for rarer cancer types.Methods: Cancer cases (N = 5,856) were selected from all children born from 1968 to 2014 and diagnosed from 1968 to 2015 in Denmark at less than 16 years of age listed in the nationwide Danish Cancer Registry. Cases were individually matched to controls (1: 100) on sex and year of birth with a total of 585,594 controls randomly sampled from all live births in Denmark from the Danish Central Population Registry. Parental age at child's birth was extracted from the Central Population Registry. Conditional logistic regression models were used to estimate odds ratios for the association between parental age at child's birth and childhood cancer risk. Parental age was modeled as both categorical (referent group, parents aged 25-29) and continuous per 5-year increase in age.Results: Offspring of older mothers were at an increased risk of acute lymphoblastic leukemia [OR = 1.10, 95% CI: (1.02, 1.19) per 5-year increase in age]. Older maternal age (40+) increased the risk of non-Hodgkin lymphoma [OR = 1.96, 95%CI: (1.12, 3.43)]. The risk of Wilms' tumor also appeared elevated with older paternal age [OR = 1.11, 95% CI: (0.97, 1.28) per 5-year increment in age].Conclusion: Older parental age was a risk factor for various childhood cancers in Danish children. Further investigation of the biological and social factors that may be contributing to these associations is warranted. (C) 2017 Elsevier Ltd. All rights reserved.
- Published
- 2017
26. Evaluating the benefit of PBS vs. VMAT dose distributions in terms of dosimetric sparing and robustness against inter-fraction anatomical changes for pediatric abdominal tumors
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Bas W. Raaymakers, Antje Knopf, Erik W Korevaar, Filipa Guerreiro, Charlotte L. Brouwer, Enrica Seravalli, Mario Ries, Cássia O. Ribeiro, Geert O. Janssens, Baudouin Denis de Senneville, Cornel Zachiu, John H. Maduro, University Medical Center [Utrecht], University Medical Center Groningen [Groningen] (UMCG), Modélisation Mathématique pour l'Oncologie (MONC), Institut de Mathématiques de Bordeaux (IMB), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)-Institut Bergonié [Bordeaux], and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1 (UB)-Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux (Bordeaux INP)-Centre National de la Recherche Scientifique (CNRS)
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medicine.medical_treatment ,Planning target volume ,Computed tomography ,VMAT ,Re-planning ,Robust pencil beam scanning ,030218 nuclear medicine & medical imaging ,0302 clinical medicine ,Pencil-beam scanning ,Child ,medicine.diagnostic_test ,Radiotherapy Dosage ,Pediatric IGRT ,Hematology ,Cone-Beam Computed Tomography ,OPEN-LABEL ,Inter-fraction uncertainties ,CANCER ,Proton therapy ,3. Good health ,PHOTON ,Oncology ,Children abdominal tumors ,030220 oncology & carcinogenesis ,Child, Preschool ,REGISTRATION ,SENSITIVITY ,Open label ,[SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing ,RADIOTHERAPY ,Dose distribution ,MODULATED PROTON THERAPY ,03 medical and health sciences ,medicine ,Journal Article ,Humans ,Radiology, Nuclear Medicine and imaging ,WILMS-TUMOR ,OPTIMIZATION ,Inter-fraction anatomical changes ,business.industry ,TREATMENT UNCERTAINTIES ,Infant ,Volumetric modulated arc therapy ,Radiation therapy ,Abdominal Neoplasms ,Pediatric abdominal tumors ,Radiotherapy, Intensity-Modulated ,Nuclear medicine ,business - Abstract
Background and purpose: To evaluate the dosimetric sparing and robustness against inter-fraction anatomical changes between photon and proton dose distributions for children with abdominal tumors.Material and methods: Volumetric modulated arc therapy (VMAT) and intensity-modulated pencil beam scanning (PBS) proton dose distributions were calculated for 20 abdominal pediatric cases (average 3, range 1-8 years). VMAT plans were based on a full-arc while PBS plans on 2-3 posterior-oblique irradiation fields. Plans were robustly optimized on a patient-specific internal target volume (ITV) using a uniform 5 mm set-up uncertainty. Additionally, for the PBS plans a +/- 3% proton range uncertainty was accounted for. Fractional dose re-calculations were performed using the planning computed tomography (CT) deformably registered to the daily cone-beam CT (CBCT) images. Fractional doses were accumulated rigidly. Planned and CBCT accumulated VMAT and PBS dose distributions were compared using dose-volume histogram (DVH) parameters.Results: Significant better sparing of the organs at risk with a maximum reduction in the mean dose of 40% was achieved with PBS. Mean ITV DVH parameters differences between planned and CBCT accumulated dose distributions were smaller than 0.5% for both VMAT and PBS. However, the ITV coverage (V-95% > 99%) was not reached for one patient for the accumulated VMAT dose distribution.Conclusions: For pediatric patients with abdominal tumors, improved dosimetric sparing was obtained with PBS compared to VMAT. In addition, PBS delivered by posterior-oblique irradiation fields demonstrated to be robust against anatomical inter-fraction changes. Compared to PBS, daily anatomical changes proved to affect the target coverage of VMAT dose distributions to a higher extent. (C) 2019 Elsevier B.V. All rights reserved.
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- 2019
27. Wilms-tumor - Update 2007.
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Reinhard, Harald, Furtwängler, R., Graf, N., Reinhard, H, and Furtwängler, R
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ANTINEOPLASTIC agents ,CLINICAL trials ,COMBINED modality therapy ,KIDNEY tumors ,LONGITUDINAL method ,SURVIVAL ,TUMOR classification ,SURGERY - Abstract
Copyright of Der Urologe A is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2007
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28. Pan-Cancer Landscape of Aberrant DNA Methylation across Human Tumors
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Marco Mina, Douglas Hanahan, Giovanni Ciriello, Sadegh Saghafinia, and Nicolo Riggi
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0301 basic medicine ,DNA repair ,hepatocellular-carcinoma ,promoter methylation ,wilms-tumor ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Chromatin remodeling ,Epigenesis, Genetic ,03 medical and health sciences ,Cell Line, Tumor ,Neoplasms ,nf-kappa-b ,expression ,Humans ,Gene Silencing ,Cancer epigenetics ,gene ,Child ,lcsh:QH301-705.5 ,Gene ,Epigenomics ,Wnt signaling pathway ,genomic characterization ,DNA Methylation ,DNA methylation instability ,TCGA pan-cancer cohort ,aberrant DNA methylation ,cancer epigenetics ,pediatric cancer ,Pediatric cancer ,signaling pathways ,3. Good health ,comprehensive molecular characterization ,030104 developmental biology ,lcsh:Biology (General) ,DNA methylation ,Cancer research ,metastatic melanoma - Abstract
Summary: The discovery of cancer-associated alterations has primarily focused on genetic variants. Nonetheless, altered epigenomes contribute to deregulate transcription and promote oncogenic pathways. Here, we designed an algorithmic approach (RESET) to identify aberrant DNA methylation and associated cis-transcriptional changes across >6,000 human tumors. Tumors exhibiting mutations of chromatin remodeling factors and Wnt signaling displayed DNA methylation instability, characterized by numerous hyper- and hypo-methylated loci. Most silenced and enhanced genes coalesced in specific pathways including apoptosis, DNA repair, and cell metabolism. Cancer-germline antigens (CG) were frequently epigenomically enhanced and their expression correlated with response to anti-PD-1, but not anti-CTLA4, in skin melanoma. Finally, we demonstrated the potential of our approach to explore DNA methylation changes in pediatric tumors, which frequently lack genetic drivers and exhibit epigenomic modifications. Our results provide a pan-cancer map of aberrant DNA methylation to inform functional and therapeutic studies. : Saghafinia et al. present an algorithmic approach to identify cancer-associated DNA methylation changes affecting gene expression. By analyzing >6,000 adult and pediatric tumors, the authors identify numerous DNA methylation changes at gene promoters that coalesce into a few pathways and that were associated with patient prognosis and response to therapy. Keywords: aberrant DNA methylation, cancer epigenetics, DNA methylation instability, TCGA pan-cancer cohort, pediatric cancer
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- 2018
29. Leistungen der Tumorchirurgie beim kindlichen Nephroblastom
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Helmig, F.-J., Helmig, M., Devens, K., Schwaiger, M., and Schriefers, K. H.
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- 1988
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30. PAX2 expression by HHV-8–infected endothelial cells induced a proangiogenic and proinvasive phenotype
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Benedetta Bussolati, Dario Di Luca, Maria Chiara Deregibus, Stefano Buttiglieri, Giovanni Camussi, Elisabetta Caselli, and Valentina Fonsato
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SARCOMA-ASSOCIATED HERPESVIRUS ,MULTICENTRIC CASTLEMANS-DISEASE ,PRIMARY EFFUSION LYMPHOMA ,LATENTLY INFECTED-CELLS ,KAPOSIS-SARCOMA ,DNA-SEQUENCES ,APOPTOSIS RESISTANCE ,WILMS-TUMOR ,HUMAN-HERPESVIRUS-8 ,PROTEIN ,Angiogenesis ,viruses ,Apoptosis ,Mice, SCID ,Biochemistry ,Mice ,Cell Movement ,Sense (molecular biology) ,Leukocytes ,Cells, Cultured ,Chemokine CCL2 ,Neovascularization, Pathologic ,angio oncogene ,Hematology ,Transfection ,Intercellular Adhesion Molecule-1 ,Phenotype ,Drug Combinations ,Herpesvirus 8, Human ,embryonic structures ,Proteoglycans ,Collagen ,animal structures ,tumor endothelial cells ,Immunology ,Biology ,NO ,In vivo ,Cell Adhesion ,Animals ,Neoplasm Invasiveness ,RNA, Antisense ,Sarcoma, Kaposi ,Gene ,PAX2 ,Oncogene ,PAX2 Transcription Factor ,Endothelial Cells ,Cell Biology ,Embryonic stem cell ,Enzyme Activation ,body regions ,Gene Expression Regulation ,Cancer research ,Laminin ,sense organs ,Proto-Oncogene Proteins c-akt - Abstract
In the present study, we evaluated whether infection of microvascular endothelial cells (HMECs) with HHV-8 can trigger the expression of PAX2 oncogene and whether PAX2 protein is involved in HHV-8–induced transformation of HMECs. We found that HHV-8 infection induced the expression of both the PAX2 gene and PAX2 protein in HMECs but failed to induce PAX2 protein in HMECs stably transfected with PAX2 antisense (HMEC-AS). HHV-8–infected HMECs but not HMEC-AS acquired proinvasive proadhesive properties, enhanced survival and in vitro angiogenesis, suggesting a correlation between PAX2 expression and the effects triggered by HHV-8 infection. When HMEC-expressing PAX2 by stable transfection with PAX2 sense gene or by HHV-8 infection were implanted in vivo in severe combined immunodeficient (SCID) mice, enhanced angiogenesis and proliferative lesions resembling KS were observed. HHV-8–infected HMEC-AS failed to induce angiogenesis and KS-like lesions. These results suggest that the expression of PAX2 is required for the proangiogenic and proinvasive changes induced by HHV-8 infection in HMECs. In conclusion, HHV-8 infection may activate an embryonic angiogenic program in HMECs by inducing the expression of PAX2 oncogene.
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- 2008
31. DAX-1 expression in pediatric rhabdomyosarcomas. Another immunohistochemical marker useful in the diagnosis of translocation positive alveolar rhabdomyosarcoma
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Virgone, Calogero, Lalli, Enzo, Bisogno, Gianni, Lazzari, Elena, Roma, Josep, Zin, Angelica, Poli, Elena, Cecchetto, Giovanni, Dall'Igna, Patrizia, Alaggio, Rita, and Universitat Autònoma de Barcelona
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Adult ,musculoskeletal diseases ,Pathology ,medicine.medical_specialty ,Adolescent ,genetic structures ,Wilms-tumor ,lcsh:Medicine ,Chromosomal translocation ,intergroup rhabdomyosarcoma ,embryonic stem-cells ,Translocation, Genetic ,Young Adult ,Rhabdomyosarcoma ,epithelioid rhabdomyosarcoma ,Biomarkers, Tumor ,medicine ,Humans ,Child ,lcsh:Science ,nuclear receptor DAX-1 ,Multidisciplinary ,DAX-1 Orphan Nuclear Receptor ,business.industry ,lcsh:R ,infantile rhabdomyofibrosarcoma ,Infant, Newborn ,fusion status ,Infant ,CHILDRENS ONCOLOGY GROUP ,EMBRYONIC STEM-CELLS ,ADRENAL HYPOPLASIA CONGENITA ,NUCLEAR RECEPTOR DAX1 ,INTERGROUP RHABDOMYOSARCOMA ,FUSION STATUS ,INFANTILE RHABDOMYOFIBROSARCOMA ,EPITHELIOID RHABDOMYOSARCOMA ,EWS/FLI1 ONCOPROTEIN ,WILMS-TUMOR ,Histology ,Wilms' tumor ,childrens oncology group ,medicine.disease ,adrenal hypoplasia congenita ,EWS/FLI1 oncoprotein ,Child, Preschool ,Alveolar rhabdomyosarcoma ,Immunohistochemistry ,lcsh:Q ,Sarcoma ,business ,Immunostaining ,Research Article - Abstract
Objectives The aim of this study was to investigate the expression of DAX-1 in a series of pediatric rhabdomyosarcomas (RMS) with known translocation and compare it to Ap2β, known to be selectively expressed in ARMS. Design We revised a series of 71 alveolar rhabdomyosarcomas (ARMS), enrolled in the Italian Protocols RMS 79 and 96, and 23 embryonal rhabdomyosarcomas (ERMS) as controls. Before investigating Ap2β and DAX-1, ARMS were reviewed and reclassified as 48 ARMS and 23 non-ARMS. Results Translocation positive ARMS showed a characteristic Ap2β/DAX-1+ staining pattern in 78% of cases, while 76% of classic ERMS were negative for both. Ap2β alone was positive in 3.9% of RMS lacking translocation, whereas DAX-1 alone was positive in 25.4%. Conversely, 9% and 6% of translocation positive ARMS were positive only for DAX-1 or Ap2β, respectively. The 23 non-ARMS shared the same phenotype as ERMS but had a higher frequency of DAX-1 expression. Conclusions DAX-1 is less specific than Ap2β, however it is a sensitive marker for translocation positive ARMS and can be helpful in their diagnosis if used in combination with Ap2β.
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- 2015
32. Tumor risk in Beckwith-Wiedemann syndrome
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H19 ,SOMATIC MOSAICISM ,CDKN1C P57(KIP2) ,METHYLATION ,Wilms tumor ,CHILDREN ,ISOLATED HEMIHYPERPLASIA ,cancer risk ,genotype-phenotype correlation ,UNIPARENTAL DISOMY ,meta-analysis ,HEMIHYPERTROPHY ,chromosome 11p15 ,Beckwith-Wiedemann syndrome ,methylation ,PATERNAL ISODISOMY ,imprinting ,WILMS-TUMOR - Abstract
Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome associated with macroglossia, abdominal wall defects, ear anomalies, and an increased risk for embryonic tumors. Reported tumor risk estimates vary between 4% and 21%. It has been hypothesized that tumor predisposition in BWS is related to the imprinting status of the H19 and LIT1 genes on chromosome 11p15. A loss of imprinting (LOI) of H19 implies a higher tumor risk. However, a systematic analysis of available data is lacking. Therefore, we performed a review and meta-analysis of reported associations between the imprinting status of the LIT1 and H19 genes and the risk for tumor development in BWS. Five publications suitable for meta-analysis were identified by electronic database searches. Sufficient data were available for 402 out of 520 patients. Patients were divided into four groups based on the imprinting status of H19 and LIT1: group I with LOI of LIT1 (45%); group 11 with LOI of H19 (9%); group III with LOI of LIT1 and LOI of H19 (21%); and group IV with normal imprinting patterns (26%). Differences in tumor risk between groups were studied with random effects meta-analysis. Tumors occurred in 55 patients. The odds of tumor development was significantly lower in group I when compared to group 11 (OR=0.06; 95% CI: 0.02-0.21) and group III (OR= 0.12; 95% CI: 0.04-0.37). Tumor risk did not differ significantly between groups 11 and III (OR= 1.40; 95% CI: 0.56-3.50). Compared to group IV, tumor risk was significantly lower in group I (OR = 0.33; 95% CI: 0.12-0.87) and higher in groups 11 (OR = 4.0; 95% CI: 1.5-10.4) and III (OR = 2.6; 95% CI: 1.2-5.7). Tumor incidence rate for group IV was 10.6% (95% CI: 3.6-17.7). Calculated absolute risks were 3% for group 1, 43% for group 11, and 28% for group 111, respectively. No Wilms tumor was seen in group I. In total, other tumors were seen with comparable frequencies in groups I-III. The results show a strong association between a LOI of H19 and especially Wilms tumor development in BWS. (c) 2005 Wiley-Liss, Inc.
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- 2005
33. Tumor risk in Beckwith-Wiedemann syndrome: A review and meta-analysis
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Patrick Rump, Mpa Zeegers, van Ton Essen, Rijksuniversiteit Groningen, Humane Biologie, Epidemiologie, and RS: NUTRIM School of Nutrition and Translational Research in Metabolism
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medicine.medical_specialty ,Beckwith-Wiedemann Syndrome ,RNA, Untranslated ,SOMATIC MOSAICISM ,Beckwith–Wiedemann syndrome ,CHILDREN ,Biology ,cancer risk ,genotype-phenotype correlation ,UNIPARENTAL DISOMY ,Gastroenterology ,chromosome 11p15 ,Risk Factors ,Internal medicine ,Neoplasms ,Genetics ,medicine ,Macroglossia ,Humans ,WILMS-TUMOR ,Hemihypertrophy ,Genetics (clinical) ,H19 ,Models, Genetic ,CDKN1C P57(KIP2) ,Chromosomes, Human, Pair 11 ,METHYLATION ,Wilms tumor ,Membrane Proteins ,Wilms' tumor ,ISOLATED HEMIHYPERPLASIA ,medicine.disease ,Uniparental disomy ,meta-analysis ,HEMIHYPERTROPHY ,Potassium Channels, Voltage-Gated ,Meta-analysis ,Overgrowth syndrome ,RNA, Long Noncoding ,PATERNAL ISODISOMY ,medicine.symptom ,imprinting ,Kidney disease - Abstract
Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome associated with macroglossia, abdominal wall defects, ear anomalies, and an increased risk for embryonic tumors. Reported tumor risk estimates vary between 4% and 21%. It has been hypothesized that tumor predisposition in BWS is related to the imprinting status of the H19 and LIT1 genes on chromosome 11p15. A loss of imprinting (LOI) of H19 implies a higher tumor risk. However, a systematic analysis of available data is lacking. Therefore, we performed a review and meta-analysis of reported associations between the imprinting status of the LIT1 and H19 genes and the risk for tumor development in BWS. Five publications suitable for meta-analysis were identified by electronic database searches. Sufficient data were available for 402 out of 520 patients. Patients were divided into four groups based on the imprinting status of H19 and LIT1: group I with LOI of LIT1 (45%); group 11 with LOI of H19 (9%); group III with LOI of LIT1 and LOI of H19 (21%); and group IV with normal imprinting patterns (26%). Differences in tumor risk between groups were studied with random effects meta-analysis. Tumors occurred in 55 patients. The odds of tumor development was significantly lower in group I when compared to group 11 (OR=0.06; 95% CI: 0.02-0.21) and group III (OR= 0.12; 95% CI: 0.04-0.37). Tumor risk did not differ significantly between groups 11 and III (OR= 1.40; 95% CI: 0.56-3.50). Compared to group IV, tumor risk was significantly lower in group I (OR = 0.33; 95% CI: 0.12-0.87) and higher in groups 11 (OR = 4.0; 95% CI: 1.5-10.4) and III (OR = 2.6; 95% CI: 1.2-5.7). Tumor incidence rate for group IV was 10.6% (95% CI: 3.6-17.7). Calculated absolute risks were 3% for group 1, 43% for group 11, and 28% for group 111, respectively. No Wilms tumor was seen in group I. In total, other tumors were seen with comparable frequencies in groups I-III. The results show a strong association between a LOI of H19 and especially Wilms tumor development in BWS. (c) 2005 Wiley-Liss, Inc.
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- 2005
34. Disruption of a novel ectodermal neural cortex 1 antisense gene, ENC-1AS and identification of ENC-1 overexpression in hairy cell leukemia
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Mikael Lerner, Marianne Hammarsund, Monika Jansson, Martin Corcoran, Olle Sangfelt, Stefan Einhorn, Chaoyong Zhu, Mats Merup, Dan Grandér, Gösta Gahrton, Hanneke C. Kluin-Nelemans, Faculteit Medische Wetenschappen/UMCG, Damage and Repair in Cancer Development and Cancer Treatment - 1, and Stem Cell Aging Leukemia and Lymphoma
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EXPRESSION ,Gene isoform ,Candidate gene ,Tumor suppressor gene ,HUMAN-CHROMOSOME 13Q14 ,ACTIN-BINDING PROTEIN ,TUMOR-SUPPRESSOR GENE ,Sandhoff disease ,Biology ,Exon ,Hexosaminidase B ,TRANSCRIPTS ,Genetics ,medicine ,Humans ,WILMS-TUMOR ,Molecular Biology ,Gene ,In Situ Hybridization, Fluorescence ,Genetics (clinical) ,DNA Primers ,Leukemia, Hairy Cell ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,CHRONIC LYMPHOCYTIC-LEUKEMIA ,Microfilament Proteins ,Neuropeptides ,Nuclear Proteins ,General Medicine ,Blotting, Northern ,medicine.disease ,Null allele ,Molecular biology ,beta-N-Acetylhexosaminidases ,HEXB ,Blotting, Southern ,Karyotyping ,Chromosomes, Human, Pair 5 ,RNA ,NUCLEAR-MATRIX PROTEIN ,INTERFERON-ALPHA - Abstract
Karyotypical alteration of chromosome 5 and in particular band 5q13 is a frequent finding in hairy cell leukemia (HCL). We have previously identified a number of candidate genes localized in close proximity to a constitutional inv(5)(p13.1q13.3) breakpoint in one HCL patient. These included beta-hexosaminodase HEXB, frequently mutated in the lysosomal storage disorder Sandhoff disease. We now report that the 5q13.3 breakpoint disrupts a novel evolutionary conserved alternative isoform of HEXB. This isoform directly overlaps, in a cis-antisense fashion, exon 1 of the gene for ectodermal neuronal cortex 1 ENC-1, and was thus named ENC-1AS. ENC-1 has previously been shown to be overexpressed in several malignancies, and is believed to play a critical regulatory role in malignant transformation of various tumors. Importantly, subsequent analysis of ENC-1 in purified primary HCL tumor cells revealed a striking upregulation of ENC-1 in all 26 patients examined, compared with normal peripheral blood lymphocytes from healthy donors. Upon further analysis of the ENC-1/ENC-1AS locus, we identified a complex 5' regulatory mechanism involving an inverse expression of the ENC-1 sense and the ENC-1AS transcripts in several tissues supporting the hypothesis that expression of ENC-1AS regulates ENC-1 levels. In addition, we have also found tissue-specific methylation of a 1.2 kb segment encompassing the overlapping ENC-1/ENC-1AS 5' exons, adding to the complexity of the regulation of this locus. Altogether, these results suggest that upregulation of ENC-1 contributes to the development of HCL and provides new information on the possible dysregulation of ENC-1 including expression of a novel antisense gene, ENC-1AS.
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- 2004
35. Denys-Drash-Syndrom: Erlanger Erfahrungen am Beispiel zweier Fallberichte
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Zugor, V., Zenker, M., Dötsch, J., Schrott, K. M., and Schott, G. E.
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- 2005
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36. Nephroblastom — Wilms-Tumor: Genetik, radiologische Diagnostik und Therapiekonzept — eine Übersicht
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Furtwängler, R., Schenk, J.-P., Reinhard, H., Leuschner, I., Rübe, C., von Schweinitz, D., and Graf, N.
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- 2005
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37. Differenzierung der Komponenten des Wilms-Tumor im Kinder- und Jugendalter von den Komponenten der Nephroblastomatose
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Kamke, Stephanie, Leuschner, Ivo, and Naumann, Carsten Maik
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doctoral thesis ,Abschlussarbeit ,Wilms-Tumor ,Wnt-Signalweg ,ddc:610 ,ddc:6XX ,Beta-Catenin ,Nephroblastomatose - Abstract
Es wurde versucht anhand von retrospektiven Präparaten aus dem Kindertumorregister der Sektion Kinderpathologie der Christian von Albrechts Universität zu Kiel, welche im Rahmen der GPOH-Nephroblastomstudie behandelt werden, eine immunhistochemische Unterscheidung von Wilms-Tumoren und der Nephroblastomatose zu finden, um die Therapie anzupassen. Die Vorläuferläsion des Wilms-Tumors, die sogenannte Nephroblastomatose ist im Gegensatz zum eigentlich Tumor benigne, sodass auf eine Chemotherapie verzichtet werden könnte. Dazu wurden Färbungen mit 4 Antikörpern angefertigt und ausgewertet. Bei den Antikörpern handelt es sich um Mitwirkende des Wnt/β-Catenin-Pathways, und zwar β-Catenin, Axin-2, MITF und APC. Mein Hauptaugenmerk liegt auf dem Onkoprotein und Transkriptionsfaktor β-Catenin. Es wird vermutet, dass dieser Pathway an der Entstehung der Tumore beteiligt ist. In den immunhistochemischen Färbungen zeigte sich, das mittels der o.g. Antikörpern allein keine solche Differenzierung möglich ist. Außnahmen bilden die unklare (bisher noch nicht beschrieben) nukleäre Positivität von Axin 2, die es nur im eigentlichen Tumor gibt sowie die nukleäre Anfärbbarkeit des Stromas bei Tumoren mit WTX- (alle Präparate) und Beta-Catenin-Mutation (5/37 Präparaten). Letzteres spricht für eine Aktivierung des Wnt-Pathways und der damit verbundenen Transkriptionsaktivierung von Protoonkogenen. Zur weiteren Suche nach Möglichkeien der Differenzierung wären molekulargenetische Untersuchungen der Antikörper und eine Ausdehnung der Präparate auf Tumore ohne WTX-Mutation nötig.
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- 2014
38. The influence of recombinant human insulin-like growth factor-I (rhIGF-I) on cell growth and cytotoxicity of drugs in childhood rhabdomyosarcoma cell lines and xenograft models
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EXPRESSION ,MICE ,FACTOR RECEPTOR ,REGENERATION ,HUMAN NEUROBLASTOMA ,cytotoxicity ,VINCRISTINE NEUROPATHY ,WILMS-TUMOR ,SCIATIC-NERVE ,vincristine ,IGF-I ,APOPTOSIS - Abstract
Purpose: Recombinant human insulin-like growth factor I (rhIGF-I) has been reported to ameliorate vincristine-induced neuropathy, the dose-limiting side effect of this antimitotic anticancer drug. However, rhIGF-I also might have adverse effects, as has been shown in vitro, where it stimulates growth of cancer cells and protects them from cytotoxicity of anticancer drugs. The influence of rhIGF-I on the cytotoxicity of vincristine has not yet been studied. Furthermore, studies performed have been done under serum-free conditions, which are far from physiological. Methods: We studied the influence of rhIGF-I on the growth of two rhabdomyosarcoma cell lines (Rh30 and Rh1) and on the antitumor effects of vincristine, cisplatin, etoposide, doxorubicin, and topotecan under serum-free and serum-containing conditions. To extend the in vitro data, we grew Rh30 cells as xenografts in mice and determined the effects of vincristine, rhIGF-I or their combination on tumor growth. Results: In vitro, both cell lines demonstrated a functional type I IGF receptor, as shown by the rapid activation of ribosomal p70 S6 kinase after stimulation with rhIGF-I. Under serum-free conditions, rhIGF-I stimulated growth of both cell lines. Exposure to cytotoxic drugs with and without rhIGF-I resulted in higher cell numbers in cultures exposed to rhIGF-I. However, relative to the appropriate control, fractional growth inhibition and or cell kill of the cytotoxic drugs was identical with and without rhIGF-I. Under serum-containing conditions, rhIGF-I had no effect on cell growth or drug cytotoxicity. In vivo we did not find a significant influence of rhIGF-I on HxRh30 cell growth, or on the antitumor activity of vincristine. Conclusions: These studies show that rhIGF-I has no adverse effects on human rhabdomyosarcoma growth or on the antitumor effect of cytotoxic drugs under serum-containing conditions in vitro or in tumor-bearing mice. Potentially, therefore, rhIGF-I may ameliorate vincristine-induced neuropathy without adversely influencing tumor growth or vincristine cytotoxicity in children.
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- 2000
39. Perlman syndrome
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cleft palate ,congenital, hereditary, and neonatal diseases and abnormalities ,renal dysplasia ,intestinal atresia ,polyhydramnios ,Wilms tumor ,haemangioma ,HAMARTOMAS ,volvulus ,MULTIPLE CONGENITAL-ANOMALIES ,FETAL GIGANTISM ,NEPHROBLASTOMATOSIS ,renal hamartomas ,hepatic fibrosis ,macrosomia ,WILMS-TUMOR ,Perlman syndrome ,FAMILIAL RENAL DYSPLASIA ,hypoglycaemia - Abstract
Perlman syndrome was first described in 1973 and comprises nephromegaly with renal dysplasia and Wilms tumor, macrosomia, cryptorchidism, and multiple facial anomalies. Polyhydramnios and hypoglycaemia are often found. Twelve children have been described from six different families. Five came from one family whose Yemenite Jewish parents were second cousins. Autosomal recessive inheritance has been suggested. Prognosis is severe with neonatal death in most children. We report on 4 new cases of Perlman syndrome from 3 families; all parents were non-consanguineous. Some of the observed manifestations have been described only once in this syndrome (cardiac defect, hepatic fibrosis with portoportal bridging, haemangioma) or never before (volvulus, intestinal atresia, and agenesis of the corpus callosum in 1 patient, a cleft palate in another). All children died within the first year. The 2 sibs were born prematurely with nephromegaly but without hamartomas or nephroblastomatosis. This is consistent with the hypothesis that dysplastic medullary parenchyma in preterm infants develops into nephroblastomatosis and hamartoma and eventually Wilms tumor. (C) 1999 Wiley-Liss, Inc.
- Published
- 1999
40. Inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene and allelic losses at chromosome arm 3p in primary renal cell carcinoma
- Subjects
endocrine system diseases ,DELETION ,HETEROZYGOSITY ,SOMATIC MUTATIONS ,urologic and male genital diseases ,T(3-8) BREAKPOINT ,female genital diseases and pregnancy complications ,REGION ,3P14.2 ,LUNG-CANCER ,LOCUS ,WILMS-TUMOR ,neoplasms ,DNA METHYLATION - Abstract
Inactivation of tumour suppressor gene(s) (TSGs) on 3p appears to be a critical event in the pathogenesis of clear cell renal cell carcinoma (CC-RCC). Analysis of loss of heterozygosity (LOH) in sporadic RCC samples has implicated roles for TSGs in three specific regions of 3p in RCC development: (1) 3p12-p14, which includes the breakpoint of the familial t(3;8) constitutional translocation involved in hereditary RCC development and a recently cloned putative TSG, the FHIT gene; (2) 3p21.2-p21.3, a common region of deletion in many cancers including lung; and (3) 3p25-p26, which contains the von Hippel-Lindau (VHL) disease TSG. We and others have shown that most primary sporadic CC-RCCs contain somatic VHL gene mutations, clearly implicating inactivation of the VHL gene in the pathogenesis of CC-RCC. It is not known if CC-RCC without VHL gene mutations have alternative mechanisms of VHL gene inactivation or result from an alternative non-VHL pathway to RCC, e.g., inactivation of TSGs in 3p12-p21. We and others have reported hypermethylation and silencing of the VHL TSG in RCC from patients with VHL disease and in CC-RCC cell lines. However, the incidence and specificity of VHL methylation in primary sporadic RCC has not been defined. Therefore, we analysed methylation of the VHL, CDKN2, MYC, and H19 genes in primary RCC samples. Hypermethylation of the VHL promoter region was detected in 11% (11/99) of the primary RCCs analysed. In 10 of these tumours, there was no evidence of concomitant VHL gene mutation. VHL methylation was specific to CC-RCC (15%, 7/45) but was not detected in any non-CC tumours (n = 16). None of the 11 RCCs methylated at VHL had evidence of methylation at either CDKN2 or MYC (methylation at CDKN2 was, however, detected in 3%, or 1/33, of RCCs without VHL methylation). A normal methylation pattern at H19 was demonstrated in the three RCCs with methylated VHL analysed. Previous studies have suggested that, in addition to VHL, other 3p TSGs at 3p12-p14 and 3p21 may be involved in CC-RCC tumourigenesis. However, the interpretation of these studies has been difficult because information on VHL gene status has not been available for these data sets. Therefore, we investigated a subset of 55 sporadic RCCs (of known VHL gene methylation and mutation status) for LOH at polymorphic markers close to candidate TSG loci in the 3p14.2 and 3p21.2-p21.3 regions. Among tumours with LOH at one or more 3p markers, the incidence of 3p25 allele loss was higher in tumours with VHL alterations (mutation or methylation) than in those without. For tumours without detectable VHL alterations, the frequency of 3p14-p21 LOH was significantly higher than the frequency of 3p25-p26 LOH (93%, 13/14 vs. 43%, 6/14; P = 0.013), whereas, in RCC samples with VHL methylation or mutation, the frequency of 3p14-p21 LOH did not differ from that of 3p25-p26 (72%, 18/25 vs. 59%, 13/22; P = 0.376). None of the 11 RCCs with 3p25 allele loss that were informative at 3p21 and 3p14 showed LOH at 3p25 only. These findings suggest that (I) VHL methylation is a specific and important event in the pathogenesis of CC-RCC; (2) in CC-RCC with 3p LOH but without VHL inactivation, mutations in TSGs at 3p14-p21 appear to have a primary role in tumourigenesis; and (3) inactivation of other 3p TSGs in addition to VHL may also be required for malignant transformation in tumours with VHL gene inactivation. (C) 1998 Wiley-Liss, Inc.
- Published
- 1998
41. Cytogenetic and molecular analysis of cellular atypical mesoblastic nephroma
- Subjects
WILMS-TUMOR - Abstract
Cytogenetic and molecular analyses were performed on three cellular (atypical) congenital mesoblastic nephromas (CMNs). Two cases had trisomy 11; in one, it was the sole karyotypic abnormality, and the other had additional numerical changes as well as an isochromosome for the long arm of chromosome I. Markers for the 11p13 and 11p15 loci were present in three copies in these two CMNs. In the third CMN, two apparently normal copies of chromosome I I were present together with additional numerical and structural chromosome changes. Because loss of heterozygosity was observed for both 11p13 and 11p15 markers, we assume that mitotic recombination occurred. Duplication and loss of imprinting of genes at 11p15 has also been observed frequently in Wilms' tumor. We therefore propose that CMN and Wilms' tumor might share common genetic pathways. (C) 1998 Wiley-Liss, Inc.
- Published
- 1998
42. Carcinoid in a horseshoe kidney - Morphology, immunohistochemistry, and cytogenetics
- Subjects
endocrine system ,WILMS-TUMOR ,neoplasms - Abstract
Renal carcinoids are very rare neoplasms. We were able to culture and subsequently karyotype a carcinoid located in the isthmus of a horseshoe kidney, which revealed the following chromosomal pattern: 47,XX, + 13[8]/46,XX,t(13;14) (q31;q11.2)[5]/46,XX[2]. The DNA index was 1. Our results, compared with the sparse data from the literature, suggest that carcinoid of the kidney has no cytogenetic aberrations in common with carcinoids from other anatomical sites reported. On the other hand, numerical and structural aberrations of chromosome 13 seem to play a crucial role in the development of metanephric-derived renal tumors.
- Published
- 1995
43. Phenotype, cancer risk, and surveillance in Beckwith-Wiedemann syndrome depending on molecular genetic subgroups
- Author
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Eamonn R. Maher, Saskia M. J. Hopman, D.J. Kadouch, Jet Bliek, Fleur Vansenne, Marcel M.A.M. Mannens, Abdulla Ibrahim, Saskia M. Maas, Johannes H. M. Merks, Raoul C.M. Hennekam, Maher, Eamonn [0000-0002-6226-6918], Apollo - University of Cambridge Repository, ANS - Complex Trait Genetics, Human Genetics, CCA -Cancer Center Amsterdam, Graduate School, Dermatology, Paediatric Oncology, ACS - Amsterdam Cardiovascular Sciences, ARD - Amsterdam Reproduction and Development, APH - Amsterdam Public Health, and Paediatric Genetics
- Subjects
0301 basic medicine ,Oncology ,Male ,Beckwith-Wiedemann Syndrome ,Beckwith–Wiedemann syndrome ,CHILDREN ,Minisatellite Repeats ,030105 genetics & heredity ,Cohort Studies ,SYNDROME BWS ,Wiedemann–Beckwith syndrome ,0302 clinical medicine ,Neoplasms ,Genotype ,ONCOLOGY-GROUP ,Young adult ,Wiedemann-Beckwith syndrome ,Child ,Genetics (clinical) ,METHYLATION ,Wilms tumor ,genotype–phenotype correlation ,Phenotype ,Potassium Channels, Voltage-Gated ,030220 oncology & carcinogenesis ,Population Surveillance ,Cohort ,Female ,RNA, Long Noncoding ,Risk ,medicine.medical_specialty ,Hepatoblastoma ,Adolescent ,ALPHA-FETOPROTEIN ,Biology ,genotype-phenotype correlation ,IDIOPATHIC HEMIHYPERTROPHY ,03 medical and health sciences ,Genomic Imprinting ,Young Adult ,neuroblastoma ,Insulin-Like Growth Factor II ,Internal medicine ,Neuroblastoma ,Genetics ,medicine ,Journal Article ,Humans ,WILMS-TUMOR ,Genetic Association Studies ,Cancer ,Wilms' tumor ,GROWTH-RATE ,DNA Methylation ,hepatoblastoma ,medicine.disease ,Immunology ,Meta-Analysis - Abstract
Patients with Beckwith-Wiedemann syndrome (BWS) have an increased risk to develop cancer in childhood, especially Wilms tumor and hepatoblastoma. The risk varies depending on the cause of BWS. We obtained clinical and molecular data in our cohort of children with BWS, including tumor occurrences, and correlated phenotype and genotype. We obtained similar data from larger cohorts reported in the literature. Phenotype, genotype and tumor occurrence were available in 229 of our own patients. Minor differences in phenotype existed depending on genotype/epigenotype, similar to earlier studies. By adding patients from the literature, we obtained data on genotype and tumor occurrence of in total 1,971 BWS patients. Tumor risks were highest in the IC1 (H19/IGF2:IG-DMR) hypermethylation subgroup (28%) and pUPD subgroup (16%) and were lower in the KCNQ1OT1:TSS-DMR (IC2) subgroup (2.6%), CDKN1C (6.9%) subgroup, and the group in whom no molecular defect was detectable (6.7%). Wilms tumors (median age 24 months) were frequent in the IC1 (24%) and pUPD (7.9%) subgroups. Hepatoblastoma occurred mostly in the pUPD (3.5%) and IC2 (0.7%) subgroups, never in the IC1 and CDKN1C subgroups, and always before 30 months of age. In the CDKN1C subgroup 2.8% of patients developed neuroblastoma. We conclude tumor risks in BWS differ markedly depending on molecular background. We propose a differentiated surveillance protocol, based on tumor risks in the various molecular subgroups causing BWS. (C) 2016 Wiley Periodicals, Inc.
- Published
- 2016
44. Radiofrequency ablation in the treatment of liver tumors in children
- Author
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Koert P. de Jong, Stijn van Laarhoven, Rienk Y. J. Tamminga, Robertine van Baren, Groningen Institute for Organ Transplantation (GIOT), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
- Subjects
Hepatoblastoma ,medicine.medical_specialty ,Pathology ,Liver tumor ,Radiofrequency ablation ,LONG-TERM ,BILIARY ATRESIA ,Wilms Tumor ,Metastasis ,law.invention ,PROGNOSTIC-FACTORS ,Wilms' tumor ,INTERNATIONAL-SOCIETY ,Biliary atresia ,law ,HEPATOCELLULAR-CARCINOMA ,medicine ,Humans ,WILMS-TUMOR ,TERM-FOLLOW-UP ,business.industry ,HEPATIC METASTASIS ,TRANSPLANTATION ,Liver Neoplasms ,General Medicine ,medicine.disease ,Kidney Neoplasms ,Transplantation ,Child, Preschool ,Hepatocellular carcinoma ,Pediatrics, Perinatology and Child Health ,Catheter Ablation ,Female ,Surgery ,Radiology ,business ,PEDIATRIC-ONCOLOGY - Abstract
Hepatoblastoma and liver metastasis of Wilms' tumors are rare hepatic tumors in children. Treatment of both tumors consists of a combination of chemotherapy and liver surgery. Radiofrequency ablation (RFA) is frequently used for the treatment of adult liver tumors but is rarely mentioned as a treatment option in pediatric liver tumors. We present a patient with hepatoblastoma and 1 with liver metastasis from a Wilms' tumor. Both patients were treated according to the latest protocols except that surgery included use of RFA. Both are well and recurrence free 8 and 3 years after surgery. Radiofrequency ablation may be a good addition to the existing arsenal of treatment modalities for pediatric liver tumors. (C) 2012 Elsevier Inc. All rights reserved.
- Published
- 2012
45. Primary Renal Soft Tissue Sarcoma in Children
- Author
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Paola Collini, Laura Morali, Gianni Bisogno, Rita Alaggio, Roberta Burnelli, Filippo Spreafico, Giovanni Cecchetto, Andrea Ferrari, Arianna Tagarelli, and Paolo Indolfi
- Subjects
Male ,medicine.medical_specialty ,Desmoplastic small-round-cell tumor ,Adolescent ,Urology ,medicine.medical_treatment ,PRIMITIVE NEUROECTODERMAL TUMOR ,WILMS-TUMOR ,KIDNEY ,IFOSFAMIDE ,ADULT ,Young Adult ,medicine ,Humans ,Rhabdomyosarcoma ,Child ,Ifosfamide ,business.industry ,Soft tissue sarcoma ,Soft tissue ,Infant ,Wilms' tumor ,Sarcoma ,medicine.disease ,Nephrectomy ,Kidney Neoplasms ,Surgery ,Radiation therapy ,Child, Preschool ,Female ,business ,medicine.drug - Abstract
Objective To describe clinical and treatment characteristics of renal soft tissue sarcomas in children, we analyzed a series of patients enrolled in the protocols coordinated by the Italian Soft Tissue Sarcoma Committee (STSC). Methods From 1979 to 2011, 2138 patients with soft tissue sarcomas were registered in different STSC protocols, and 12 had a renal sarcoma: 7 primitive peripheral neuroectodermal tumors, 2 undifferentiated sarcomas, 1 rhabdomyosarcoma, 1 desmoplastic small round cell tumor, and 1 kaposiform hemangioendothelioma. Treatment included conservative surgery, chemotherapy according to the guidelines of the protocols, and radiotherapy for high-risk patients. Results Nephrectomy was performed in 11 children resulting in a complete tumor resection in 7. In 4 patients, macroscopical (1) or microscopic (3) tumor residuals remained postoperatively. Tumorectomy was performed in patients with congenital renal agenesis. All patients received chemotherapy. Seven patients also received postoperative radiotherapy. Overall, 9 patients are alive in first complete remission with a median follow-up of 6.1 years (range, 1.3-21.1 years). Two of the 7 patients with primitive peripheral neuroectodermal tumors (pPNETs) died after an early relapse: 1 had metastatic disease at diagnosis and the other was initially misdiagnosed with Wilms tumor (WT). One child with desmoplastic small round cell tumor (DSRCT) is alive with disease. Two patients developed signs of ifosfamide-related nephrotoxicity. Conclusion In our analysis, pPNET is the most common type of renal soft tissue sarcoma (STS). Prognosis seems satisfactory with the adoption of an aggressive multidisciplinary approach, especially when complete tumor resection is possible. The replacement of ifosfamide with cyclophosphamide could be considered after nephrectomy.
- Published
- 2012
46. An integrated genome screen identifies the Wnt signaling pathway as a major target of WT1
- Author
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Aaron Golden, Thomas J. McGarry, Jonathan D. Licht, Pilib Ó Broin, Jared M. Flatow, and Marianne K.H. Kim
- Subjects
Embryo, Nonmammalian ,Transcription, Genetic ,Xenopus ,wilms-tumor ,growth suppression ,TCF/LEF family ,urologic and male genital diseases ,Promoter Regions, Genetic ,chip-chip ,kidney development ,Oligonucleotide Array Sequence Analysis ,Multidisciplinary ,Genome ,biology ,Wnt signaling pathway ,LRP6 ,LRP5 ,Biological Sciences ,CREB-Binding Protein ,female genital diseases and pregnancy complications ,TCF Transcription Factors ,microarray ,chromatin occupancy ,Protein Binding ,Signal Transduction ,congenital, hereditary, and neonatal diseases and abnormalities ,Chromatin Immunoprecipitation ,tumor suppressor ,Molecular Sequence Data ,Embryonic Development ,c-myc ,Cell Line, Tumor ,tumor-suppressor gene ,transcriptional activation ,Animals ,Genetic Testing ,CREB-binding protein ,cell-growth ,WT1 Proteins ,Transcription factor ,ctnnb1 mutations ,Binding Sites ,Base Sequence ,urogenital system ,Gene Expression Profiling ,fungi ,beta-catenin ,DNA ,biology.organism_classification ,Wnt Proteins ,Gene Expression Regulation ,biology.protein ,Cancer research ,Chromatin immunoprecipitation - Abstract
WT1, a critical regulator of kidney development, is a tumor suppressor for nephroblastoma but in some contexts functions as an oncogene. A limited number of direct transcriptional targets of WT1 have been identified to explain its complex roles in tumorigenesis and organogenesis. In this study we performed genome-wide screening for direct WT1 targets, using a combination of ChIP–ChIP and expression arrays. Promoter regions bound by WT1 were highly G-rich and resembled the sites for a number of other widely expressed transcription factors such as SP1, MAZ, and ZNF219. Genes directly regulated by WT1 were implicated in MAPK signaling, axon guidance, and Wnt pathways. Among directly bound and regulated genes by WT1, nine were identified in the Wnt signaling pathway, suggesting that WT1 modulates a subset of Wnt components and responsive genes by direct binding. To prove the biological importance of the interplay between WT1 and Wnt signaling, we showed that WT1 blocked the ability of Wnt8 to induce a secondary body axis during Xenopus embryonic development. WT1 inhibited TCF-mediated transcription activated by Wnt ligand, wild type and mutant, stabilized β-catenin by preventing TCF4 loading onto a promoter. This was neither due to direct binding of WT1 to the TCF binding site nor to interaction between WT1 and TCF4, but by competition of WT1 and TCF4 for CBP. WT1 interference with Wnt signaling represents an important mode of its action relevant to the suppression of tumor growth and guidance of development.
- Published
- 2009
47. Hypomethylation at multiple maternally methylated imprinted regions including PLAGL1 and GNAS loci in Beckwith-Wiedemann syndrome
- Author
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Silvia Russo, Rita Fischetto, Faustina Lalatta, Jet Bliek, I. Karen Temple, Flavia Cerrato, Gaetano Verde, Maria Michela Rinaldi, L. Giordano, Marcel M.A.M. Mannens, Jonathan L A Callaway, Serena Ferraiuolo, Paola Ferrari, Agostina De Crescenzo, Deborah J G Mackay, Saskia M. Maas, Maria Vittoria Cubellis, Andrea Riccio, Angela Sparago, Lidia Larizza, Bliek, J., Verde, G., Callaway, J., Maas, S., DE CRESCENZO, A., Sparago, A., Cerrato, F., Russo, S., Ferraiuolo, S., Rinaldi, M. M., Fischetto, R., Lalatta, F., Giordano, L., Ferrari, P., Cubellis, MARIA VITTORIA, Larizza, L., Temple, I. K., Mannens, M., Mackay, D. J. G., Riccio, A., Human Genetics, Paediatric Genetics, ACS - Amsterdam Cardiovascular Sciences, ARD - Amsterdam Reproduction and Development, Cerrato, Flavia, Cubellis, M. V., Temple, K., Mannes, M., Mackay, D., and Riccio, Andrea
- Subjects
Male ,Candidate gene ,Beckwith-Wiedemann Syndrome ,Wilms-tumor ,animal diseases ,Beckwith-Wiedemann syndrome (BWS) ,KCNQ1OT1 ,methylation ,imprinting ,imprinting disorder ,hypomethylation of imprinted loci (HIL) ,neonatal diabetes-mellitus ,birth-weight ,gene network ,growth ,establishment ,individuals ,mutations ,defects ,DNA Mutational Analysis ,Beckwith–Wiedemann syndrome ,Cell Cycle Proteins ,Polymerase Chain Reaction ,Article ,Genomic Imprinting ,Chromogranins ,GTP-Binding Protein alpha Subunits, Gs ,Genetics ,medicine ,GNAS complex locus ,Humans ,DNA (Cytosine-5-)-Methyltransferases ,Epigenetics ,Imprinting (psychology) ,Genetics (clinical) ,Polymorphism, Genetic ,biology ,Tumor Suppressor Proteins ,DNA Methylation ,medicine.disease ,Settore MED/03 - Genetica Medica ,DNA methylation ,biology.protein ,Female ,Genomic imprinting ,Transcription Factors - Abstract
Genomic imprinting is an epigenetic phenomenon restricting gene expression in a manner dependent on parent of origin. Imprinted gene products are critical regulators of growth and development, and imprinting disorders are associated with both genetic and epigenetic mutations, including disruption of DNA methylation within the imprinting control regions (ICRs) of these genes. It was recently reported that some patients with imprinting disorders have a more generalised imprinting defect, with hypomethylation at a range of maternally methylated ICRs. We report a cohort of 149 patients with a clinical diagnosis of Beckwith-Wiedemann syndrome (BWS), including 81 with maternal hypomethylation of the KCNQ1OT1 ICR. Methylation analysis of 11 ICRs in these patients showed that hypomethylation affecting multiple imprinted loci was restricted to 17 patients with hypomethylation of the KCNQ1OT1 ICR, and involved only maternally methylated loci. Both partial and complete hypomethylation was demonstrated in these cases, suggesting a possible postzygotic origin of a mosaic imprinting error. Some ICRs, including the PLAGL1 and GNAS/NESPAS ICRs implicated in the aetiology of transient neonatal diabetes and pseudohypoparathyroidism type 1b, respectively, were more frequently affected than others. Although we did not find any evidence for mutation of the candidate gene DNMT3L, these results support the hypotheses that trans-acting factors affect the somatic maintenance of imprinting at multiple maternally methylated loci and that the clinical presentation of these complex cases may reflect the loci and tissues affected with the epigenetic abnormalities.European Journal of Human Genetics advance online publication, 17 December 2008; doi:10.1038/ejhg.2008.233
- Published
- 2009
48. The influence of recombinant human insulin-like growth factor-I (rhIGF-I) on cell growth and cytotoxicity of drugs in childhood rhabdomyosarcoma cell lines and xenograft models
- Author
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Gidding, CEM, Germain, GS, Dilling, MB, Meeuwsen-de Boer, TGJ, Ashmun, RA, Veverka, KA, Kamps, WA, Houghton, PJ, and Faculteit Medische Wetenschappen/UMCG
- Subjects
EXPRESSION ,MICE ,FACTOR RECEPTOR ,REGENERATION ,HUMAN NEUROBLASTOMA ,cytotoxicity ,VINCRISTINE NEUROPATHY ,WILMS-TUMOR ,SCIATIC-NERVE ,vincristine ,IGF-I ,APOPTOSIS - Abstract
Purpose: Recombinant human insulin-like growth factor I (rhIGF-I) has been reported to ameliorate vincristine-induced neuropathy, the dose-limiting side effect of this antimitotic anticancer drug. However, rhIGF-I also might have adverse effects, as has been shown in vitro, where it stimulates growth of cancer cells and protects them from cytotoxicity of anticancer drugs. The influence of rhIGF-I on the cytotoxicity of vincristine has not yet been studied. Furthermore, studies performed have been done under serum-free conditions, which are far from physiological. Methods: We studied the influence of rhIGF-I on the growth of two rhabdomyosarcoma cell lines (Rh30 and Rh1) and on the antitumor effects of vincristine, cisplatin, etoposide, doxorubicin, and topotecan under serum-free and serum-containing conditions. To extend the in vitro data, we grew Rh30 cells as xenografts in mice and determined the effects of vincristine, rhIGF-I or their combination on tumor growth. Results: In vitro, both cell lines demonstrated a functional type I IGF receptor, as shown by the rapid activation of ribosomal p70 S6 kinase after stimulation with rhIGF-I. Under serum-free conditions, rhIGF-I stimulated growth of both cell lines. Exposure to cytotoxic drugs with and without rhIGF-I resulted in higher cell numbers in cultures exposed to rhIGF-I. However, relative to the appropriate control, fractional growth inhibition and or cell kill of the cytotoxic drugs was identical with and without rhIGF-I. Under serum-containing conditions, rhIGF-I had no effect on cell growth or drug cytotoxicity. In vivo we did not find a significant influence of rhIGF-I on HxRh30 cell growth, or on the antitumor activity of vincristine. Conclusions: These studies show that rhIGF-I has no adverse effects on human rhabdomyosarcoma growth or on the antitumor effect of cytotoxic drugs under serum-containing conditions in vitro or in tumor-bearing mice. Potentially, therefore, rhIGF-I may ameliorate vincristine-induced neuropathy without adversely influencing tumor growth or vincristine cytotoxicity in children.
- Published
- 2000
49. Relaxation of Insulin-like growth factor-2 imprinting and discordant methylation at KvDMR1 in two first-cousins affected by Beckwith-Wiedemann and Klippel-Trenaunay-Weber syndromes
- Author
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SPERANDEO MP, UNGARO P, VERNUCCI M, PEDONE PV, CERRATO F, PERONE L, CASOLA S, CUBELLIS, MARIA VITTORIA, SEBASTIO G, RICCIO A., BRUNI, CARMELO BRUNO, ANDRIA, GENEROSO, Sperandeo, Mp, Ungaro, P, Vernucci, M, Pedone, Pv, Cerrato, F, Perone, L, Casola, S, Cubellis, MARIA VITTORIA, Bruni, CARMELO BRUNO, Andria, Generoso, Sebastio, G, and Riccio, A.
- Subjects
EXPRESSION ,H19 GENE ,MICE ,HUMAN CANCER ,HISTONE ACETYLATION ,HUMAN IGF2R GENE ,WILMS-TUMOR ,FACTOR-II GENE ,DNA METHYLATION ,POLYMORPHISM - Abstract
Beckwith-Wiedeman syndrome (BWS) and Klippel-Trenaunay-Weber syndrome (KTWS) are different human disorders characterized, among other features, by tissue overgrowth. Deregulation of one or more imprinted genes located at chromosome 11p15.5, of which insulin-like growth factor 2 (IGF2) is the most likely candidate, is believed to cause BWS, whereas the etiology of KTWS is completely obscure. We report a case of BWS and a case of KTWS in a single family. The probands, sons of two sisters, showed relaxation of the maternal IGF2 imprinting, although they inherited different 11p15.5 alleles from their mothers and did not show any chromosome rearrangement. The patient with BWS also displayed hypomethylation at KvDMR1, a maternally methylated CpG island within an intron of the KvLQT1 gene. The unaffected brother of the BWS proband shared the same maternal and paternal 11p15.5 haplotype with his brother, but the KvDMR1 locus was normally methylated. Methylation of the H19 gene was normal in both the BWS and KTWS probands. Linkage between the insulin-like growth factor 2 receptor (IGF2R) gene and the tissue overgrowth was also excluded. These results raise the possibility that a defective modifier or regulatory gene unlinked to 11p15.5 caused a spectrum of epigenetic alterations in the germ line or early development of both cousins, ranging from the relaxation of IGF2 imprinting in the KTWS proband to disruption of both the imprinted expression of IGF2 and the imprinted methylation of KvDMR1 in the BWS proband. Analysis of these data also indicates that loss of IGF2 imprinting is not necessarily linked to alteration of methylation at the KvDMR1 or H19 loci and supports the notion that IGF2 overexpression is involved in the etiology of the tissue hypertrophy observed in different overgrowth disorders, including KTWS.
- Published
- 2000
50. Perlman syndrome: Four additional cases and review
- Author
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Richard A. van Lingen, Hetty Th. Henneveld, Antonie J. van Essen, Irene Stolte-Dijkstra, and Ben C.J. Hamel
- Subjects
medicine.medical_specialty ,Polyhydramnios ,Pediatrics ,congenital, hereditary, and neonatal diseases and abnormalities ,renal dysplasia ,intestinal atresia ,haemangioma ,HAMARTOMAS ,volvulus ,Internal medicine ,NEPHROBLASTOMATOSIS ,medicine ,renal hamartomas ,Hamartoma ,hepatic fibrosis ,Perlman syndrome ,macrosomia ,WILMS-TUMOR ,Agenesis of the corpus callosum ,Nephroblastomatosis ,Genetics (clinical) ,FAMILIAL RENAL DYSPLASIA ,cleft palate ,business.industry ,Intestinal atresia ,polyhydramnios ,Wilms tumor ,Wilms' tumor ,medicine.disease ,MULTIPLE CONGENITAL-ANOMALIES ,Endocrinology ,FETAL GIGANTISM ,Nephromegaly ,medicine.symptom ,business ,hypoglycaemia - Abstract
Perlman syndrome was first described in 1973 and comprises nephromegaly with renal dysplasia and Wilms tumor, macrosomia, cryptorchidism, and multiple facial anomalies. Polyhydramnios and hypoglycaemia are often found. Twelve children have been described from six different families. Five came from one family whose Yemenite Jewish parents were second cousins. Autosomal recessive inheritance has been suggested. Prognosis is severe with neonatal death in most children. We report on 4 new cases of Perlman syndrome from 3 families; all parents were non-consanguineous. Some of the observed manifestations have been described only once in this syndrome (cardiac defect, hepatic fibrosis with portoportal bridging, haemangioma) or never before (volvulus, intestinal atresia, and agenesis of the corpus callosum in 1 patient, a cleft palate in another). All children died within the first year. The 2 sibs were born prematurely with nephromegaly but without hamartomas or nephroblastomatosis. This is consistent with the hypothesis that dysplastic medullary parenchyma in preterm infants develops into nephroblastomatosis and hamartoma and eventually Wilms tumor. (C) 1999 Wiley-Liss, Inc.
- Published
- 1999
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