7,278 results match your criteria Childhood Cancer Genetics


Antibody Response to COVID-19 mRNA Vaccine in Patients With Lung Cancer After Primary Immunization and Booster: Reactivity to the SARS-CoV-2 WT Virus and Omicron Variant.

J Clin Oncol 2022 Jun 27:JCO2102986. Epub 2022 Jun 27.

Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA.

Purpose: To examine COVID-19 mRNA vaccine-induced binding and neutralizing antibody responses in patients with non-small-cell lung cancer (NSCLC) to SARS-CoV-2 614D (wild type [WT]) strain and variants of concern after the primary 2-dose and booster vaccination.

Methods: Eighty-two patients with NSCLC and 53 healthy volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2-specific binding and neutralizing antibody responses were evaluated by Meso Scale Discovery assay and live virus Focus Reduction Neutralization Assay, respectively. Read More

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Contribution of Cyclin-dependent Kinase Inhibitor 1B Genotypes to Childhood Leukemia Risk.

In Vivo 2022 Jul-Aug;36(4):1637-1642

Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan, R.O.C.;

Background/aim: Although genetic differences in cell-cycle control genes have been associated with cancer risk, to our knowledge, no report has specifically examined the role of gene variants in childhood acute lymphoblastic leukemia (ALL). Cyclin-dependent kinase inhibitor 1B (CDKN1B; also known as p27/KIP1) is a cell-cycle regulating gene. This study aimed at investigating the association between CDKN1B genotypes and childhood ALL risk. Read More

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MacroH2As regulate enhancer-promoter contacts affecting enhancer activity and sensitivity to inflammatory cytokines.

Cell Rep 2022 Jun;39(12):110988

Cancer and Leukaemia Epigenetics and Biology Program, Josep Carreras Leukaemia Research Institute (IJC), Campus ICO-GTP-UAB, Badalona, Barcelona 08916, Spain; Program for Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP), Badalona, Barcelona 08916, Spain. Electronic address:

MacroH2A histone variants have a function in gene regulation that is poorly understood at the molecular level. We report that macroH2A1.2 and macroH2A2 modulate the transcriptional ground state of cancer cells and how they respond to inflammatory cytokines. Read More

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MYCN induces cell-specific tumorigenic growth in RB1-proficient human retinal organoid and chicken retina models of retinoblastoma.

Oncogenesis 2022 Jun 21;11(1):34. Epub 2022 Jun 21.

Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden.

Retinoblastoma is a rare, intraocular paediatric cancer that originates in the neural retina and is most frequently caused by bi-allelic loss of RB1 gene function. Other oncogenic mutations, such as amplification and increased expression of the MYCN gene, have been found even with proficient RB1 function. In this study, we investigated whether MYCN over-expression can drive carcinogenesis independently of RB1 loss-of-function mutations. Read More

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Hypoxia-inducible lentiviral gene expression in engineered human macrophages.

J Immunother Cancer 2022 Jun;10(6)

Mozart Therapeutics, Seattle, Washington, USA

Background: Human immune cells, including monocyte-derived macrophages, can be engineered to deliver proinflammatory cytokines, bispecific antibodies, and chimeric antigen receptors to support immune responses in different disease settings. When gene expression is regulated by constitutively active promoters, lentiviral payload gene expression is unregulated, and can result in potentially toxic quantities of proteins. Regulated delivery of lentivirally encoded proteins may allow localized or conditional therapeutic protein expression to support safe delivery of adoptively transferred, genetically modified cells with reduced capacity for systemic toxicities. Read More

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Editorial.

Cancer Genet 2022 Jun 7;266-267:37-38. Epub 2022 Jun 7.

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

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Clonal heterogeneity and rates of specific chromosome gains are risk predictors in childhood high-hyperdiploid B-cell acute lymphoblastic leukemia.

Mol Oncol 2022 Jun 21. Epub 2022 Jun 21.

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

B-cell acute lymphoblastic leukemia (B-ALL) is the commonest childhood cancer. High hyperdiploidy (HHD) identifies the most frequent cytogenetic subgroup in childhood B-ALL. Although hyperdiploidy represents an important prognostic factor in childhood B-ALL, the specific chromosome gains with prognostic value in HHD-B-ALL remain controversial, and the current knowledge about the hierarchy of chromosome gains, clonal heterogeneity and chromosomal instability in HHD-B-ALL remains very limited. Read More

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Clinical and Molecular Features of Pediatric Cancer Patients with Lynch Syndrome.

Pediatr Blood Cancer 2022 Jun 17:e29859. Epub 2022 Jun 17.

Department of Pediatrics, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX.

Background: The association of childhood cancer with Lynch syndrome is not established compared with the significant pediatric cancer risk in recessive constitutional mismatch repair deficiency syndrome (CMMRD).

Procedure: We describe the clinical features, germline analysis, and tumor genomic profiling of patients with Lynch syndrome among patients enrolled in pediatric cancer genomic studies.

Results: There were 6 of 773 (0. Read More

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Genome Wide Association Study of Pregnancy in Childhood Cancer Survivors: A Report from the Childhood Cancer Survivor Study.

Cancer Epidemiol Biomarkers Prev 2022 Jun 14. Epub 2022 Jun 14.

University of Alabama at Birmingham, Birmingham, AL, United States.

Background: Gonadotoxic treatment-related infertility has a significant impact on quality of life in childhood cancer survivors. Genome-wide association analyses to delineate the risk of infertility in childhood cancer survivors have not been previously reported.

Methods: Leveraging genotype data from a large survivor cohort, the Childhood Cancer Survivor Study (CCSS), we investigated the role of Single Nucleotide Polymorphisms (SNPs) on future pregnancy or siring a pregnancy in survivors without pelvic, testicular, or brain radiation who had ever been married. Read More

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Meta-analysis of epigenome-wide association studies in newborns and children show widespread sex differences in blood DNA methylation.

Mutat Res Rev Mutat Res 2022 Jan-Jun;789:108415. Epub 2022 Mar 14.

University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands.

Background: Among children, sex-specific differences in disease prevalence, age of onset, and susceptibility have been observed in health conditions including asthma, immune response, metabolic health, some pediatric and adult cancers, and psychiatric disorders. Epigenetic modifications such as DNA methylation may play a role in the sexual differences observed in diseases and other physiological traits.

Methods: We performed a meta-analysis of the association of sex and cord blood DNA methylation at over 450,000 CpG sites in 8438 newborns from 17 cohorts participating in the Pregnancy And Childhood Epigenetics (PACE) Consortium. Read More

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Leukopenia, macrocytosis, and thrombocytopenia occur in young adults with Down syndrome.

Gene 2022 Jun 8;835:146663. Epub 2022 Jun 8.

International Research Center for Medical Sciences, Kumamoto University, Japan; Cancer Science Institute of Singapore, National University of Singapore, Singapore; Department of Pediatrics, National University of Singapore, Singapore. Electronic address:

Down syndrome (DS) is a common congenital disorder caused by trisomy 21. Due to the increase in maternal age with population aging and advances in medical treatment for fatal complications in their early childhood, the prevalence and life expectancy of DS individuals have greatly increased. Despite this rise in the number of DS adults, their hematological status remains poorly examined. Read More

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Mutations in ALK signaling pathways conferring resistance to ALK inhibitor treatment lead to collateral vulnerabilities in neuroblastoma cells.

Mol Cancer 2022 Jun 10;21(1):126. Epub 2022 Jun 10.

Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universität Berlin, Kelchstr.31, 12169, Berlin, Germany.

Background: Development of resistance to targeted therapies has tempered initial optimism that precision oncology would improve poor outcomes for cancer patients. Resistance mechanisms, however, can also confer new resistance-specific vulnerabilities, termed collateral sensitivities. Here we investigated anaplastic lymphoma kinase (ALK) inhibitor resistance in neuroblastoma, a childhood cancer frequently affected by activating ALK alterations. Read More

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The immune cell atlas of human neuroblastoma.

Cell Rep Med 2022 Jun 9;3(6):100657. Epub 2022 Jun 9.

Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, 171 77 Stockholm, Sweden. Electronic address:

Understanding the complete immune cell composition of human neuroblastoma (NB) is crucial for the development of immunotherapeutics. Here, we perform single-cell RNA sequencing (scRNA-seq) on 19 human NB samples coupled with multiplex immunohistochemistry, survival analysis, and comparison with normal fetal adrenal gland data. We provide a comprehensive immune cell landscape and characterize cell-state changes from normal tissue to NB. Read More

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Complex Elucidation of Cells-of-Origin in Pediatric Soft Tissue Sarcoma: From Concepts to Real Life, Hide-and-Seek through Epigenetic and Transcriptional Reprogramming.

Int J Mol Sci 2022 Jun 4;23(11). Epub 2022 Jun 4.

Childhood Cancer & Cell Death (C3), LabEx DEVweCAN, Centre Léon Bérard, Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, 69008 Lyon, France.

Soft tissue sarcoma (STS) comprise a large group of mesenchymal malignant tumors with heterogeneous cellular morphology, proliferative index, genetic lesions and, more importantly, clinical features. Full elucidation of this wide diversity remains a central question to improve their therapeutic management and the identity of cell(s)-of-origin from which these tumors arise is part of this enigma. Cellular reprogramming allows transitions of a mature cell between phenotypes, or identities, and represents one key driver of tumoral heterogeneity. Read More

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Understanding the Underlying Molecular Mechanisms of Meiotic Arrest during In Vitro Spermatogenesis in Rat Prepubertal Testicular Tissue.

Int J Mol Sci 2022 May 24;23(11). Epub 2022 May 24.

INSERM, U1239, Adrenal and Gonadal Pathophysiology Team, Laboratory of Neuroendocrine Endocrine and Germinal Differentiation and Communication, Rouen University Hospital, Rouen Normandy University, 76000 Rouen, France.

In vitro spermatogenesis appears to be a promising approach to restore the fertility of childhood cancer survivors. The rat model has proven to be challenging, since germ cell maturation is arrested in organotypic cultures. Here, we report that, despite a meiotic entry, abnormal synaptonemal complexes were found in spermatocytes, and in vitro matured rat prepubertal testicular tissues displayed an immature phenotype. Read More

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Underdiagnosis and Undertreatment of Modifiable Cardiovascular Risk Factors Among Survivors of Childhood Cancer.

J Am Heart Assoc 2022 Jun 8;11(12):e024735. Epub 2022 Jun 8.

University of Alberta Edmonton Alberta Canada.

Background Determine the prevalence and predictors associated with underdiagnosis and undertreatment of modifiable cardiovascular disease (CVD) risk factors (hypertension, dyslipidemia, glucose intolerance/diabetes) among adult survivors of childhood cancer at high risk of premature CVD. Methods and Results This was a cross-sectional study of adult-aged survivors of childhood cancer treated with anthracyclines or chest radiotherapy, recruited across 9 US metropolitan regions. Survivors completed questionnaires and in-home clinical assessments. Read More

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Risk of cancer in young and older patients with congenital heart disease and the excess risk of cancer by syndromes, organ transplantation and cardiac surgery: Swedish health registry study (1930-2017).

Lancet Reg Health Eur 2022 Jul 29;18:100407. Epub 2022 May 29.

Institute of Medicine, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.

Background: Increasing survival of patients with congenital heart disease (CHD) will result in an increased risk of age-dependent acquired diseases later in life. We aimed to investigate the risk of cancer in young and older patients with CHD and to evaluate the excess risk of cancer by syndromes, organ transplantation and cardiac surgery.

Methods: Patients with CHD born between 1930 and 2017 were identified using Swedish Health Registers. Read More

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Accelerated epigenetic aging in newborns with Down syndrome.

Aging Cell 2022 Jun 6:e13652. Epub 2022 Jun 6.

Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.

Accelerated aging is a hallmark of Down syndrome (DS), with adults experiencing early-onset Alzheimer's disease and premature aging of the skin, hair, and immune and endocrine systems. Accelerated epigenetic aging has been found in the blood and brain tissue of adults with DS but when premature aging in DS begins remains unknown. We investigated whether accelerated aging in DS is already detectable in blood at birth. Read More

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Genetic predisposition to central nervous system tumors in children - what the neurosurgeon should know.

Acta Neurochir (Wien) 2022 Jun 3. Epub 2022 Jun 3.

The Pediatric Oncology Research Laboratory, Department of Pediatrics and Adolescent Medicine, Rigshospitalet University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark.

Background: Historically, few pediatric central nervous system (CNS) tumors were thought to result from genetic predisposition. However, within the last decade, new DNA sequencing methods have led to an increased recognition of high-risk cancer predisposition syndromes in children with CNS tumors. Thus, genetic predisposition is increasingly impacting clinical pediatric neuro-oncology. Read More

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Shared environment and colorectal cancer: A Nordic pedigree registry-based cohort study.

Int J Cancer 2022 Jun 3. Epub 2022 Jun 3.

Medical Diagnostics Karolinska, Karolinska University Hospital, Stockholm, Sweden.

Risk of colorectal cancer (CRC) increases in relatives of patients with CRC. The extent to which this is attributable to genetic predisposition or shared environment is unclear. We explored this question using nationwide cohorts from Denmark, Finland and Sweden. Read More

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Autoantibodies to Zinc Transporter 8 and Genotype in Type 1 Diabetes Childhood: A Pioneering Study in North Africa.

J Diabetes Res 2022 23;2022:2539871. Epub 2022 May 23.

Autoimmunity, Cancer, And Immunogenetics Research Laboratory, University Hospital Habib Bourguiba of Sfax, Tunisia.

Background: Type 1 diabetes (T1D) occurs as a result of insulin deficiency due to destructive lesions of pancreatic cells. In addition to classical autoantibodies (Abs) to islet cell antigens, antizinc transporter 8 Abs (ZnT8-Ab) have been recently described in T1D.

Objective: As no data on ZnT8-Ab in Tunisian patients has been reported, we aim to evaluate the relationships between ZnT8-Ab, ZnT8 coding gene () promoter polymorphism, and T1D risk in newly diagnosed children. Read More

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Alphabetti kinase Spaghetti: the complex roles of IKKα and β in the canonical NF-κB pathway.

Authors:
Neil D Perkins

Biochem J 2022 Jun;479(11):1121-1126

Newcastle University Biosciences Institute, Wolfson Childhood Cancer Research Centre, Newcastle University, Level 6, Herschel Building, Brewery Lane, Newcastle upon Tyne NE1 7RU, U.K.

Numerous studies, published over many years, have established the key role that the IκB kinase (IKK) subunits, α and β, play in regulating the Nuclear Factor κB (NF-κB) pathway. This research generally concluded that their functions can be separated, with IKKβ being the critical regulator of the canonical NF-κB pathway, while IKKα functions as the key activating kinase for the non-canonical pathway. However, other roles for these kinases have been described and several reports concluded that this separation of their functions may not always be the case. Read More

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tumors, but not tumor-derived cell lines, are adrenergic lineage, GD2+, and responsive to anti-GD2 antibody therapy.

Oncoimmunology 2022 24;11(1):2075204. Epub 2022 May 24.

Division of Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Neuroblastoma is a commonly lethal solid tumor of childhood and intensive chemoradiotherapy treatment cures ~50% of children with high-risk disease. The addition of immunotherapy using dinutuximab, a monoclonal antibody directed against the GD2 disialoganglioside expressed on neuroblasts, improves survival when incorporated into front-line therapy and shows robust activity in regressing relapsed disease when combined with chemotherapy. Still, many children succumb to neuroblastoma progression despite receiving dinutuximab-based immunotherapy, and efforts to counteract the immune suppressive signals responsible are warranted. Read More

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Relationship between Bax and Bcl-2 Protein Expression and Outcome of Induction Phase Chemotherapy in Pediatric Acute Lymphoblastic Leukemia.

Asian Pac J Cancer Prev 2022 May 1;23(5):1679-1685. Epub 2022 May 1.

Hematology Oncology Division, Department of Child Health, Faculty of Medicine, Universitas Airlangga/Dr. Soetomo General Academic Hospital, Surabaya, Indonesia.

Background: Overexpression of the antiapoptotic protein Bcl-2 causes apoptosis to stop and conversely the increased expression of the proapoptotic protein Bax makes lymphoblasts easy to destroy. The Bax/Bcl-2 ratio plays a role in the balance of apoptosis, immortality, resistance, and outcome of chemotherapy. We analyzed the relationship between the Bax/BCl-2 ratio and the outcome of induction phase chemotherapy in pediatric Acute Lymphoblastic Leukemia (ALL). Read More

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Discovery of potent BET bromodomain 1 stereoselective inhibitors using DNA-encoded chemical library selections.

Proc Natl Acad Sci U S A 2022 May 27;119(22):e2122506119. Epub 2022 May 27.

Center for Drug Discovery, Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030.

SignificanceBET bromodomain inhibition is therapeutic in multiple diseases; however, pan-BET inhibitors have induced significant myelosuppression and gastrointestinal toxicity, perhaps due to inhibition of both tandem bromodomains (BD) of all BET family members. However, selective inhibition of just the first BD (BD1) phenocopies pan-BET inhibitor activity in preclinical models of cancer, other diseases, and, for BRDT, in the testes for a contraceptive effect. Here, we leveraged our multibillion-molecule collection of DNA-encoded chemical libraries (DECLs) to identify BET BD1-selective inhibitors of specific chirality with high potency, stability, and good cellular activity. Read More

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Maternal and prenatal factors and age at thelarche in the LEGACY Girls Study cohort: implications for breast cancer risk.

Int J Epidemiol 2022 May 25. Epub 2022 May 25.

Department of Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA.

Background: Earlier onset of breast development (thelarche) is associated with increased breast cancer risk. Identifying modifiable factors associated with earlier thelarche may provide an opportunity for breast cancer risk reduction starting early in life, which could especially benefit girls with a greater absolute risk of breast cancer due to family history.

Methods: We assessed associations of maternal pre-pregnancy body mass index (BMI), physical activity during pregnancy, gestational weight gain and daughters' weight and length at birth with age at thelarche using longitudinal Weibull models in 1031 girls in the Lessons in Epidemiology and Genetics of Adult Cancer from Youth (LEGACY) Girls Study-a prospective cohort of girls, half of whom have a breast cancer family history (BCFH). Read More

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Acute lymphoblastic leukemia displays a distinct highly methylated genome.

Nat Cancer 2022 Jun 19;3(6):768-782. Epub 2022 May 19.

Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.

DNA methylation is tightly regulated during development and is stably maintained in healthy cells. In contrast, cancer cells are commonly characterized by a global loss of DNA methylation co-occurring with CpG island hypermethylation. In acute lymphoblastic leukemia (ALL), the commonest childhood cancer, perturbations of CpG methylation have been reported to be associated with genetic disease subtype and outcome, but data from large cohorts at a genome-wide scale are lacking. Read More

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[Practical Education Program in Precision Cancer Medicine].

Authors:
Kiyoshi Miyagawa

Gan To Kagaku Ryoho 2022 May;49(5):525-528

Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo.

To train medical staffs capable of practicing precision cancer medicine, The University of Tokyo and 5 universities in the Kanto area planned the education program consisting of a variety of scientific fields including genomic science and have offered educational opportunities to graduate school students. The program aiming to facilitate students' knowledge and practical skills in this field is closely connected with the expert panel of cancer genomic medicine in which multidisciplinary medical staffs discuss novel therapeutic choices based on patients' genomic information in the incurable cases lacking standard treatments. Education programs focusing on the treatment of rare cancers as well as childhood and adolescent cancers are also based on multidisciplinary collaborations. Read More

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Recurrent Germline Variant in Predisposes Children to Lymphoblastic Leukemia or Lymphoma.

Int J Mol Sci 2022 May 5;23(9). Epub 2022 May 5.

Tettamanti Research Center, Pediatrics, University of Milan Bicocca, Fondazione MBBM/San Gerardo Hospital, 20900 Monza, Italy.

Somatic loss of function mutations in cohesin genes are frequently associated with various cancer types, while cohesin disruption in the germline causes cohesinopathies such as Cornelia-de-Lange syndrome (CdLS). Here, we present the discovery of a recurrent heterozygous germline aberration at amino acid position 298 (p.P298S/A) identified in three children with lymphoblastic leukemia or lymphoma in a total dataset of 482 pediatric cancer patients. Read More

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