5,385 results match your criteria Childhood Cancer Genetics


Co-targeting of BCL2 with venetoclax and MCL1 with S63845 is synthetically lethal in relapsed mantle cell lymphoma.

Clin Cancer Res 2019 Apr 19. Epub 2019 Apr 19.

Institute of Pathological Physiology and First Dept. of Medicine- Hematology, Charles University General Hospital and First Faculty of Medicine

Purpose: Mantle cell lymphoma (MCL) is an aggressive subtype of B-cell non-Hodgkin lymphomas characterized by (over)expression of BCL2. A BCL2-targeting drug venetoclax (VTX) has promising anticancer activity in MCL. We analyzed molecular mechanisms of VTX resistance in MCL cells, and tested strategies to overcome it. Read More

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http://dx.doi.org/10.1158/1078-0432.CCR-18-3275DOI Listing

Genome sequencing analysis of blood cells identifies germline haplotypes strongly associated with drug resistance in osteosarcoma patients.

BMC Cancer 2019 Apr 16;19(1):357. Epub 2019 Apr 16.

Inova Children's Hospital, Falls Church, VA, USA.

Background: Osteosarcoma is the most common malignant bone tumor in children. Survival remains poor among histologically poor responders, and there is a need to identify them at diagnosis to avoid delivering ineffective therapy. Genetic variation contributes to a wide range of response and toxicity related to chemotherapy. Read More

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http://dx.doi.org/10.1186/s12885-019-5474-yDOI Listing
April 2019
1 Read

Family History of Breast Cancer Associated with Breast Cancer in Survivors of Hodgkin Lymphoma.

Int J Cancer Clin Res 2019 25;6(1). Epub 2019 Feb 25.

Huntsman Cancer Institute, The University of Utah, USA.

Introduction: Advances in treatments for Hodgkin Lymphoma (HL) have significantly increased survival of childhood and adult patients; however, the leading cause of death in HL survivors is due to secondary malignancy following HL treatment [1,2]. Among women treated for HL, breast cancer (BC) is the most common secondary malignancy [3]. We explored if an association exists between HL and BC exists within families. Read More

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http://dx.doi.org/10.23937/2378-3419/1410107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6455954PMC
February 2019
1 Read

Epigenetic silencing of SOCS5 potentiates JAK-STAT signaling and progression of T-cell acute lymphoblastic leukemia.

Cancer Sci 2019 Apr 11. Epub 2019 Apr 11.

Department of Pediatrics, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.

Activating mutations in cytokine receptors and transcriptional regulators govern aberrant signal transduction in T-cell lineage acute lymphoblastic leukemia (T-ALL). However, the roles played by suppressors of cytokine signaling remain incompletely understood. We examined the regulatory roles of SOCS5 in T-ALL cellular signaling networks and leukemia progression. Read More

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http://dx.doi.org/10.1111/cas.14021DOI Listing
April 2019
1 Read

A Nonsmoker Man in His 40s With a Diagnosis of Genetic-Related Idiopathic Pulmonary Fibrosis (Surfactant-Protein C Gene Mutation).

Chest 2019 Apr;155(4):e91-e96

Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padova, Padova, Italy. Electronic address:

A nonsmoker man in his 40s underwent bilateral lung transplantation with a referral diagnosis of genetic-related idiopathic pulmonary fibrosis (IPF). The patient had no medical history in childhood and early adulthood, nor was there a family history of IPF. His nonsmoker father presented with lung cancer at 59 years of age. Read More

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http://dx.doi.org/10.1016/j.chest.2018.12.015DOI Listing
April 2019
2 Reads

An update on the central nervous system manifestations of DICER1 syndrome.

Acta Neuropathol 2019 Apr 5. Epub 2019 Apr 5.

Department of Pathology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Ave, Bader 104, Boston, MA, 02115, USA.

DICER1 syndrome is a rare tumor predisposition syndrome with manifestations that predominantly affect children and young adults. The syndrome is typically caused by heterozygous germline loss-of-function DICER1 alterations accompanied on the other allele by somatic missense mutations occurring at one of a few mutation hotspots within the sequence encoding the RNase IIIb domain. DICER1 encodes a member of the microRNA biogenesis machinery. Read More

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http://dx.doi.org/10.1007/s00401-019-01997-yDOI Listing
April 2019
2 Reads

Parental Education and Genetics of BMI from Infancy to Old Age: A Pooled Analysis of 29 Twin Cohorts.

Obesity (Silver Spring) 2019 Apr 5. Epub 2019 Apr 5.

Department of Public Health, University of Helsinki, Helsinki, Finland.

Objective: The objective of this study was to analyze how parental education modifies the genetic and environmental variances of BMI from infancy to old age in three geographic-cultural regions.

Methods: A pooled sample of 29 cohorts including 143,499 twin individuals with information on parental education and BMI from age 1 to 79 years (299,201 BMI measures) was analyzed by genetic twin modeling.

Results: Until 4 years of age, parental education was not consistently associated with BMI. Read More

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http://dx.doi.org/10.1002/oby.22451DOI Listing
April 2019
4 Reads
3.734 Impact Factor

Proteogenomics and Hi-C reveal transcriptional dysregulation in high hyperdiploid childhood acute lymphoblastic leukemia.

Nat Commun 2019 04 3;10(1):1519. Epub 2019 Apr 3.

Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, SE-221 84, Lund, Sweden.

Hyperdiploidy, i.e. gain of whole chromosomes, is one of the most common genetic features of childhood acute lymphoblastic leukemia (ALL), but its pathogenetic impact is poorly understood. Read More

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http://dx.doi.org/10.1038/s41467-019-09469-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447538PMC
April 2019
1 Read

The Pediatric Cell Atlas: Defining the Growth Phase of Human Development at Single-Cell Resolution.

Dev Cell 2019 Apr 28;49(1):10-29. Epub 2019 Mar 28.

Department of Biomedical Informatics, University of Cincinnati College of Medicine, and Cincinnati Children's Hospital Medical Center, Division of Biomedical Informatics, Cincinnati, OH 45229, USA.

Single-cell gene expression analyses of mammalian tissues have uncovered profound stage-specific molecular regulatory phenomena that have changed the understanding of unique cell types and signaling pathways critical for lineage determination, morphogenesis, and growth. We discuss here the case for a Pediatric Cell Atlas as part of the Human Cell Atlas consortium to provide single-cell profiles and spatial characterization of gene expression across human tissues and organs. Such data will complement adult and developmentally focused HCA projects to provide a rich cytogenomic framework for understanding not only pediatric health and disease but also environmental and genetic impacts across the human lifespan. Read More

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http://dx.doi.org/10.1016/j.devcel.2019.03.001DOI Listing
April 2019
3 Reads

De Novo and Inherited Pathogenic Variants in KDM3B Cause Intellectual Disability, Short Stature, and Facial Dysmorphism.

Am J Hum Genet 2019 Apr 28;104(4):758-766. Epub 2019 Mar 28.

Department of Human Genetics, Radboud University Medical Center, 6525GA Nijmegen, the Netherlands; Princess Máxima Center for Pediatric Oncology, 3584CS Utrecht, the Netherlands; Department of Genetics, University Medical Center Utrecht, 3508AB Utrecht, the Netherlands. Electronic address:

By using exome sequencing and a gene matching approach, we identified de novo and inherited pathogenic variants in KDM3B in 14 unrelated individuals and three affected parents with varying degrees of intellectual disability (ID) or developmental delay (DD) and short stature. The individuals share additional phenotypic features that include feeding difficulties in infancy, joint hypermobility, and characteristic facial features such as a wide mouth, a pointed chin, long ears, and a low columella. Notably, two individuals developed cancer, acute myeloid leukemia and Hodgkin lymphoma, in childhood. Read More

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http://dx.doi.org/10.1016/j.ajhg.2019.02.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451728PMC
April 2019
1 Read

Genomic subtyping and therapeutic targeting of acute erythroleukemia.

Nat Genet 2019 04 29;51(4):694-704. Epub 2019 Mar 29.

Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Acute erythroid leukemia (AEL) is a high-risk leukemia of poorly understood genetic basis, with controversy regarding diagnosis in the spectrum of myelodysplasia and myeloid leukemia. We compared genomic features of 159 childhood and adult AEL cases with non-AEL myeloid disorders and defined five age-related subgroups with distinct transcriptional profiles: adult, TP53 mutated; NPM1 mutated; KMT2A mutated/rearranged; adult, DDX41 mutated; and pediatric, NUP98 rearranged. Genomic features influenced outcome, with NPM1 mutations and HOXB9 overexpression being associated with a favorable prognosis and TP53, FLT3 or RB1 alterations associated with poor survival. Read More

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http://dx.doi.org/10.1038/s41588-019-0375-1DOI Listing
April 2019
1 Read
29.352 Impact Factor

Target identification reveals lanosterol synthase as a vulnerability in glioma.

Proc Natl Acad Sci U S A 2019 Apr 28;116(16):7957-7962. Epub 2019 Mar 28.

Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University, New York, NY 10065;

Diffuse intrinsic pontine glioma (DIPG) remains an incurable childhood brain tumor for which novel therapeutic approaches are desperately needed. Previous studies have shown that the menin inhibitor MI-2 exhibits promising activity in preclinical DIPG and adult glioma models, although the mechanism underlying this activity is unknown. Here, using an integrated approach, we show that MI-2 exerts its antitumor activity in glioma largely independent of its ability to target menin. Read More

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http://dx.doi.org/10.1073/pnas.1820989116DOI Listing
April 2019
2 Reads

Incidence of and Risk Factors for Histologically Confirmed Solid Benign Tumors Among Long-term Survivors of Childhood Cancer.

JAMA Oncol 2019 Mar 28. Epub 2019 Mar 28.

Department of Pediatric Oncology, Emma Children's Hospital, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam, the Netherlands.

Importance: Survivors of childhood cancer (CCSs) face risk of developing subsequent tumors. Solid benign tumors may be cancer precursors; benign tumors and cancers may share etiologic factors. However, comprehensive data on the risk for solid benign tumors are lacking. Read More

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http://dx.doi.org/10.1001/jamaoncol.2018.6862DOI Listing
March 2019
3 Reads

Dicer1 phospho-mimetic promotes tumor progression and dissemination.

Cancer Res 2019 Mar 26. Epub 2019 Mar 26.

Genetics, The University of Texas MD Anderson Cancer Center

Dicer1 functions as a tumor suppressor in mouse models. In humans, somatic mutations are associated with many cancers in adults and DICER1 syndrome patients with DICER1 germline mutations are susceptible to childhood cancers. Dicer is phosphorylated by the ERK-MAP kinase pathway and since this pathway is activated in human cancers, we asked whether phosphorylated Dicer1 contributed to tumor development. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-2460DOI Listing

Risk variants disrupting enhancers of T1 and T cells in type 1 diabetes.

Proc Natl Acad Sci U S A 2019 Apr 25;116(15):7581-7590. Epub 2019 Mar 25.

Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA 19104;

Genome-wide association studies (GWASs) have revealed 59 genomic loci associated with type 1 diabetes (T1D). Functional interpretation of the SNPs located in the noncoding region of these loci remains challenging. We perform epigenomic profiling of two enhancer marks, H3K4me1 and H3K27ac, using primary T1 and T cells isolated from healthy and T1D subjects. Read More

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http://dx.doi.org/10.1073/pnas.1815336116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462079PMC
April 2019
9.809 Impact Factor

Genetic Determinants of Ototoxicity During and After Childhood Cancer Treatment: Protocol for the PanCareLIFE Study.

JMIR Res Protoc 2019 Mar 19;8(3):e11868. Epub 2019 Mar 19.

Princess Maxima Center for Pediatric Oncology, Utrecht, Netherlands.

Background: Survival rates after childhood cancer now reach nearly 80% in developed countries. However, treatments that lead to survival and cure can cause serious adverse effects with lifelong negative impacts on survivor quality of life. Hearing impairment is a common adverse effect in children treated with cisplatin-based chemotherapy or cranial radiotherapy. Read More

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http://dx.doi.org/10.2196/11868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6444213PMC
March 2019
3 Reads

Identification of new Wilms tumour predisposition genes: an exome sequencing study.

Lancet Child Adolesc Health 2019 May 16;3(5):322-331. Epub 2019 Mar 16.

Division of Genetics and Epidemiology, Institute of Cancer Research, London, UK; Cancer Genetics Unit, Royal Marsden NHS Foundation Trust, London, UK. Electronic address:

Background: Wilms tumour is the most common childhood renal cancer and is genetically heterogeneous. While several Wilms tumour predisposition genes have been identified, there is strong evidence that further predisposition genes are likely to exist. Our study aim was to identify new predisposition genes for Wilms tumour. Read More

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http://dx.doi.org/10.1016/S2352-4642(19)30018-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472290PMC
May 2019
2 Reads

Multiple tumors due to mosaic genome-wide paternal uniparental disomy.

Pediatr Blood Cancer 2019 Jun 18;66(6):e27715. Epub 2019 Mar 18.

Department of Pediatrics, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.

Mosaic genome-wide paternal uniparental disomy is an infrequently described disorder in which affected individuals have signs and symptoms that may resemble Beckwith-Wiedemann syndrome. In addition, they can develop multiple benign and malignant tumors throughout life. Routine molecular diagnostics may not detect the (characteristic) low level of mosaicism, and the diagnosis is likely to be missed. Read More

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http://dx.doi.org/10.1002/pbc.27715DOI Listing

MC1R variants in childhood and adolescent melanoma: a retrospective pooled analysis of a multicentre cohort.

Lancet Child Adolesc Health 2019 May 12;3(5):332-342. Epub 2019 Mar 12.

Molecular and Pharmaco-Epidemiology Unit, Department of Experimental Oncology, European Institute of Oncology IRCCS, Milan, Italy. Electronic address:

Background: Germline variants in the melanocortin 1 receptor gene (MC1R) might increase the risk of childhood and adolescent melanoma, but a clear conclusion is challenging because of the low number of studies and cases. We assessed the association of MC1R variants with childhood and adolescent melanoma in a large study comparing the prevalence of MC1R variants in child or adolescent patients with melanoma to that in adult patients with melanoma and in healthy adult controls.

Methods: In this retrospective pooled analysis, we used the M-SKIP Project, the Italian Melanoma Intergroup, and other European groups (with participants from Australia, Canada, France, Greece, Italy, the Netherlands, Serbia, Spain, Sweden, Turkey, and the USA) to assemble an international multicentre cohort. Read More

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http://dx.doi.org/10.1016/S2352-4642(19)30005-7DOI Listing
May 2019
5 Reads

DNA damage signalling from the placenta to foetal blood as a potential mechanism for childhood leukaemia initiation.

Sci Rep 2019 Mar 13;9(1):4370. Epub 2019 Mar 13.

School of Clinical Science, University of Bristol, Learning and Research Centre, Southmead Hospital, Bristol, UK.

For many diseases with a foetal origin, the cause for the disease initiation remains unknown. Common childhood acute leukaemia is thought to be caused by two hits, the first in utero and the second in childhood in response to infection. The mechanism for the initial DNA damaging event are unknown. Read More

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http://dx.doi.org/10.1038/s41598-019-39552-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416312PMC
March 2019
2 Reads

Cell-free tumour DNA testing for early detection of cancer - a potential future tool.

J Intern Med 2019 Mar 12. Epub 2019 Mar 12.

Clinical Genetics, Karolinska University Hospital Solna, Stockholm, Sweden.

In recent years, detection of cell-free tumour DNA (ctDNA) or liquid biopsy has emerged as an attractive noninvasive methodology to detect cancer-specific genetic aberrations in plasma, and numerous studies have reported on the feasibility of ctDNA in advanced cancer. In particular, ctDNA assays can capture a more 'global' portrait of tumour heterogeneity, monitor therapy response, and lead to early detection of resistance mutations. More recently, ctDNA analysis has also been proposed as a promising future tool for detection of early cancer and/or cancer screening. Read More

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http://dx.doi.org/10.1111/joim.12897DOI Listing

Anatomic Origin of Osteochondrogenic Progenitors Impacts Sensitivity to EWS-FLI1-Induced Transformation.

Cancers (Basel) 2019 Mar 6;11(3). Epub 2019 Mar 6.

Department of Pediatrics, University of Michigan, Ann Arbor, MI 48109, USA.

Ewing sarcomas predominantly arise in pelvic and stylopod bones (i.e., femur and humerus), likely as a consequence of oncogene-induced transformation of mesenchymal stem/progenitor cells (MSCs). Read More

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http://dx.doi.org/10.3390/cancers11030313DOI Listing

Association of Promoter Polymorphisms With the Risk of Childhood Leukemia.

Anticancer Res 2019 Mar;39(3):1185-1190

Department of Physiology, China Medical University, Taichung, Taiwan, R.O.C.

Background/aim: The association of matrix metalloproteinase-2 (MMP-2) genotypes with adult leukemia has been reported only once, but never for childhood leukemia. This study aimed to determine the role of MMP-2 promoter -1306 (rs243865) and -735 (rs2285053) genotypes in childhood leukemia risk.

Materials And Methods: This case-control study included 266 patients and 266 age- and gender-matched healthy controls. Read More

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http://dx.doi.org/10.21873/anticanres.13228DOI Listing
March 2019
1 Read

Enigmatic gender difference in cancer incidence: evidences from childhood cancers.

Am J Epidemiol 2019 Mar 5. Epub 2019 Mar 5.

State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.

We aimed to investigate the differences in cancer incidence between boys and girls. The incidence data for pediatric cancer were retrieved from the International Incidence of Childhood Cancer. Poisson regression was applied to detect the gender differences in cancer incidence at global and regional levels. Read More

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https://academic.oup.com/aje/advance-article/doi/10.1093/aje
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http://dx.doi.org/10.1093/aje/kwz058DOI Listing
March 2019
8 Reads
5.230 Impact Factor

Outcomes of patients with childhood B-cell precursor acute lymphoblastic leukaemia with late bone marrow relapses: long-term follow-up of the ALLR3 open-label randomised trial.

Lancet Haematol 2019 Apr 27;6(4):e204-e216. Epub 2019 Feb 27.

Childrens Cancer Group, Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; Tata Translational Cancer Research Centre, Tata Medical Center, New Town, Kolkata, India. Electronic address:

Background: The ALLR3 trial investigated outcomes of children with B-cell precursor acute lymphoblastic leukaemia who had late bone marrow relapses. We analysed long-term follow-up outcomes of these patients.

Methods: ALLR3 was an open-label randomised clinical trial that recruited children aged 1-18 years with B-cell precursor acute lymphoblastic leukaemia who had late bone marrow relapses. Read More

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http://dx.doi.org/10.1016/S2352-3026(19)30003-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445853PMC
April 2019
2 Reads

Sex ratio among childhood cancers by single year of age.

Pediatr Blood Cancer 2019 Jun 28;66(6):e27620. Epub 2019 Feb 28.

Division of Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.

Background: The male excess in childhood cancer incidence is well-established; however, the underlying biologic mechanisms remain unknown. Examining the association between male sex and childhood cancer by single year of age and tumor type may highlight important periods of risk such as variation in growth and hormonal changes, which will inform etiologic hypotheses.

Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER) 18 registries (2000-2015), incidence rate ratios (IRR) and 95% confidence intervals (95% CI) were estimated as the measure of association between male sex and childhood cancer by single year of age (0-19). Read More

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http://dx.doi.org/10.1002/pbc.27620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6472964PMC
June 2019
3 Reads

Reproductive factors, exogenous hormone use and incidence of melanoma among women in the United States.

Br J Cancer 2019 Apr 28;120(7):754-760. Epub 2019 Feb 28.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, U.S. Department of Health and Human Services, Rockville, MD, USA.

Background: Although the photosensitising effects of oestrogens may increase the impact of ultraviolet radiation (UVR) on melanoma risk, few prospective studies have comprehensively assessed the association between oestrogen-related factors and melanoma.

Methods: We examined the associations between reproductive factors, exogenous oestrogen use and first primary invasive melanoma among 167 503 non-Hispanic white, postmenopausal women in the NIH-AARP Diet and Health Study. Satellite-based ambient UVR estimates were linked to geocoded residential locations of participants at study baseline. Read More

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http://dx.doi.org/10.1038/s41416-019-0411-zDOI Listing
April 2019
4 Reads

Primary Immunodeficiency and Cancer Predisposition Revisited: Embedding Two Closely Related Concepts Into an Integrative Conceptual Framework.

Authors:
Oskar A Haas

Front Immunol 2018 12;9:3136. Epub 2019 Feb 12.

Department of Clinical Genetics, Children's Cancer Research Institute, Vienna, Austria.

Common understanding suggests that the normal function of a "healthy" immune system safe-guards and protects against the development of malignancies, whereas a genetically impaired one might increase the likelihood of their manifestation. This view is primarily based on and apparently supported by an increased incidence of such diseases in patients with specific forms of immunodeficiencies that are caused by high penetrant gene defects. As I will review and discuss herein, such constellations merely represent the tip of an iceberg. Read More

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https://www.frontiersin.org/article/10.3389/fimmu.2018.03136
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http://dx.doi.org/10.3389/fimmu.2018.03136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6379258PMC
February 2019
7 Reads

Multidisciplinary analysis of pediatric T-ALL: 9q34 gene fusions.

Cancer Genet 2019 Feb 12;231-232:1-13. Epub 2018 Dec 12.

Laboratory Corporation of America, 1904 TW Alexander Drive, Research Triangle Park, NC 27709, United States. Electronic address:

T-cell acute lymphoblastic leukemia (T-ALL) is not as frequently reported as the B-cell counterpart (B-ALL), only occurring in about 15% of pediatric cases with a typically heterogeneous etiology. Approximately 8% of childhood T-ALL cases have rearrangements involving the ABL1 tyrosine kinase gene at 9q34.12; although a t(9;22), resulting in a fusion of ABL1 with the BCR gene at 22q11. Read More

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http://dx.doi.org/10.1016/j.cancergen.2018.12.002DOI Listing
February 2019

EED and EZH2 constitutive variants: A study to expand the Cohen-Gibson syndrome phenotype and contrast it with Weaver syndrome.

Am J Med Genet A 2019 Apr 21;179(4):588-594. Epub 2019 Feb 21.

Department of Clinical Genetics, St George's University of London, London, United Kingdom.

Overgrowth-intellectual disability (OGID) syndromes are characterized by increased growth (height and/or head circumference ≥+2 SD) in association with an intellectual disability. Constitutive EED variants have previously been reported in five individuals with an OGID syndrome, eponymously designated Cohen-Gibson syndrome and resembling Weaver syndrome. Here, we report three additional individuals with constitutive EED variants, identified through exome sequencing of an OGID patient series. Read More

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http://dx.doi.org/10.1002/ajmg.a.61066DOI Listing
April 2019
1 Read

Bi-allelic Variants in TONSL Cause SPONASTRIME Dysplasia and a Spectrum of Skeletal Dysplasia Phenotypes.

Am J Hum Genet 2019 Mar 14;104(3):422-438. Epub 2019 Feb 14.

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

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http://dx.doi.org/10.1016/j.ajhg.2019.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6408318PMC
March 2019
3 Reads
10.931 Impact Factor

Predictors of residential mobility and its impact on air pollution exposure among children diagnosed with early childhood leukemia.

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

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http://dx.doi.org/10.1038/s41370-019-0126-5DOI Listing
February 2019

Hyperthyroidism Following Radiation Therapy for Childhood Cancer: A Report from the Childhood Cancer Survivor Study.

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

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https://linkinghub.elsevier.com/retrieve/pii/S03603016193020
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http://dx.doi.org/10.1016/j.ijrobp.2019.02.009DOI Listing
February 2019
10 Reads

Medulloblastoma.

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

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http://dx.doi.org/10.1038/s41572-019-0063-6DOI Listing
February 2019
9 Reads

Haploinsufficiency of UNC13D increases the risk of lymphoma.

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

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http://dx.doi.org/10.1002/cncr.32011DOI Listing
February 2019

Fibroblast growth factor receptor signaling in pediatric B-cell precursor acute lymphoblastic leukemia.

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

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http://dx.doi.org/10.1038/s41598-018-38169-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372586PMC
February 2019
1 Read

Drug sensitivity testing on patient-derived sarcoma cells predicts patient response to treatment and identifies c-Sarc inhibitors as active drugs for translocation sarcomas.

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

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http://dx.doi.org/10.1038/s41416-018-0359-4DOI Listing
February 2019
6 Reads

Pediatric malignancies in neurofibromatosis type 1: A population-based cohort study.

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

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http://dx.doi.org/10.1002/ijc.32187DOI Listing
February 2019
3 Reads

Hyperinsulinemic hypoglycemia in seven patients with de novo NSD1 mutations.

Am J Med Genet A 2019 Apr 4;179(4):542-551. 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

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http://dx.doi.org/10.1002/ajmg.a.61062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454923PMC
April 2019
10 Reads

Beckwith-Wiedemann syndrome in diverse populations.

Am J Med Genet A 2019 Apr 4;179(4):525-533. 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

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http://dx.doi.org/10.1002/ajmg.a.61053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454922PMC
April 2019
4 Reads

Aneuploidy in children with relapsed B-cell precursor acute lymphoblastic leukaemia: clinical importance of detecting a hypodiploid origin of relapse.

Br J Haematol 2019 Apr 3;185(2):266-283. 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

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http://dx.doi.org/10.1111/bjh.15770DOI Listing
April 2019
5 Reads

Incidence and survival of central nervous system tumors in childhood and adolescence in Girona (Spain) 1990-2013: national and international comparisons.

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

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http://dx.doi.org/10.1007/s12094-019-02043-9DOI Listing
February 2019

Postmenopausal osteoporotic fracture-associated COLIA1 variant impacts bone accretion in girls.

Bone 2019 Apr 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

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https://linkinghub.elsevier.com/retrieve/pii/S87563282193003
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http://dx.doi.org/10.1016/j.bone.2019.01.026DOI Listing
April 2019
12 Reads

Hematologic malignancies and Li-Fraumeni syndrome.

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

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http://molecularcasestudies.cshlp.org/lookup/doi/10.1101/mcs
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http://dx.doi.org/10.1101/mcs.a003210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371746PMC
February 2019
22 Reads

Hematopoietic stem cell transplantation in children and adolescents with relapsed or refractory B-cell non-Hodgkin lymphoma.

Int J Hematol 2019 Apr 30;109(4):483-490. Epub 2019 Jan 30.

Department of Pediatrics, Yamagata University School of Medicine, Yamagata, Japan.

We undertook a retrospective study using the national registry data of hematopoietic stem cell transplantation (HSCT) in Japan to investigate the effect of graft source, particularly autologous or allogeneic tissue, on the treatment outcome in patients aged less than 18 years with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL). Survival analysis was conducted on 31 autologous HSCT (auto-HSCT) and 48 allogeneic HSCT (allo-HSCT) recipients between 1990 and 2013. The 5-year survival rates were significantly lower for allo-HSCT compared to auto-HSCT recipients (32% vs. Read More

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http://dx.doi.org/10.1007/s12185-019-02608-yDOI Listing
April 2019
2 Reads

The lysine-specific methyltransferase KMT2C/MLL3 regulates DNA repair components in cancer.

EMBO Rep 2019 Mar 21;20(3). 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

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http://dx.doi.org/10.15252/embr.201846821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399616PMC
March 2019
1 Read

Author Correction: Genome-wide association study identifies susceptibility loci for B-cell childhood acute lymphoblastic leukemia.

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

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http://www.nature.com/articles/s41467-018-08106-9
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http://dx.doi.org/10.1038/s41467-018-08106-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341085PMC
January 2019
12 Reads
10.742 Impact Factor

Metabolic syndrome as cardiovascular risk factor in childhood cancer survivors.

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

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https://linkinghub.elsevier.com/retrieve/pii/S10408428183020
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http://dx.doi.org/10.1016/j.critrevonc.2018.10.010DOI Listing
January 2019
11 Reads