383 results match your criteria Osteosarcoma Variants


Selective Activation of ZAK β Expression by 3-Hydroxy-2-Phenylchromone Inhibits Human Osteosarcoma Cells and Triggers Apoptosis via JNK Activation.

Int J Mol Sci 2020 May 9;21(9). Epub 2020 May 9.

Graduate Institute of Biomedical Science, China Medical University, Taichung 404, Taiwan.

Although various advancements in radical surgery and neoadjuvant chemotherapy have been developed in treating osteosarcoma (OS), their clinical prognosis remains poor. A synthetic chemical compound, 3-hydroxylflavone, that is reported to regulate ROS production is known to inhibit human bone osteosarcoma cells. However, its role and mechanism in human OS cells remains unclear. Read More

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http://dx.doi.org/10.3390/ijms21093366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247666PMC
May 2020
2.862 Impact Factor

Isolated diaphragmatic metastasis from periosteal osteosarcoma of the humerus: a case report.

J Cardiothorac Surg 2020 Apr 16;15(1):61. Epub 2020 Apr 16.

Department of Thoracic Surgery, Peking Union Medical College Hospital, CAMS & PUMC, No 1 Shuaifuyuan, Beijing, 100730, China.

Background: Isolated diaphragmatic metastasis is rarely associated with periosteal osteosarcoma.

Case Presentation: A 24-year-old female patient was found to have periosteal osteosarcoma of the right humerus 11 years ago. Computed tomography showed a mass in her left chest in 2018, and thoracotomy was performed to remove the tumour. Read More

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http://dx.doi.org/10.1186/s13019-020-01103-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164283PMC

Genomics and Therapeutic Vulnerabilities of Primary Bone Tumors.

Cells 2020 Apr 14;9(4). Epub 2020 Apr 14.

IRCCS Istituto Ortopedico Rizzoli, Laboratory of Experimental Oncology, via di Barbiano 1/10, 40136 Bologna, Italy.

Osteosarcoma, Ewing sarcoma and chondrosarcoma are rare diseases but the most common primary tumors of bone. The genes directly involved in the sarcomagenesis, tumor progression and treatment responsiveness are not completely defined for these tumors, and the powerful discovery of genetic analysis is highly warranted in the view of improving the therapy and cure of patients. The review summarizes recent advances concerning the molecular and genetic background of these three neoplasms and, of their most common variants, highlights the putative therapeutic targets and the clinical trials that are presently active, and notes the fundamental issues that remain unanswered. Read More

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http://dx.doi.org/10.3390/cells9040968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227002PMC

Cisplatin Resistance in Osteosarcoma: Validation of Candidate DNA Repair-Related Therapeutic Targets and Drugs for Tailored Treatments.

Front Oncol 2020 10;10:331. Epub 2020 Mar 10.

IRCCS Istituto Ortopedico Rizzoli, Laboratory of Experimental Oncology, Pharmacogenomics and Pharmacogenetics Research Unit, Bologna, Italy.

Treatment of high-grade osteosarcoma, the most common malignant tumor of bone, is largely based on administration of cisplatin and other DNA damaging drugs. Altered DNA repair mechanisms may thus significantly impact on either response or resistance to chemotherapy. In this study, by using a panel of human osteosarcoma cell lines, either sensitive or resistant to cisplatin, we assessed the value as candidate therapeutic targets of DNA repair-related factors belonging to the nucleotide excision repair (NER) or base excision repair (BER) pathways, as well as of a group of 18 kinases, which expression was higher in cisplatin-resistant variants compared to their parental cell lines and may be indirectly involved in DNA repair. Read More

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http://dx.doi.org/10.3389/fonc.2020.00331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077033PMC

Prominent entrapment of respiratory epithelium in primary and metastatic intrapulmonary non-epithelial neoplasms: a frequent morphological pattern closely mimicking adenofibroma and other biphasic pulmonary lesions.

Virchows Arch 2020 Mar 19. Epub 2020 Mar 19.

Institute of Pathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), University Hospital, Krankenhausstrasse 8-10, 91054, Erlangen, Germany.

As one of the most common target organs for hematogenous spread from diverse cancers, biopsy interpretation of lung tumors is complicated by the challenging question of primary versus metastatic and by frequent entrapment of native respiratory glands. Nevertheless, the literature dealing with this issue is surprisingly sparse and no single study has been devoted to this topic. We reviewed 47 surgical lung specimens of non-epithelial neoplasms (38 metastases, mainly from sarcomas and 9 primary lesions) for frequency and pattern of intralesional epithelial entrapment. Read More

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http://dx.doi.org/10.1007/s00428-020-02796-7DOI Listing

Experimental Study of Somatic Variants of Osteosarcoma by Whole-Exome Sequencing.

Med Sci Monit 2020 Mar 20;26:e920826. Epub 2020 Mar 20.

Department of Bone and Soft Tissue Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan, China (mainland).

BACKGROUND This study aimed to investigate the role of gene mutation site distribution, biological function, pathway enrichment, and gene association analysis in the occurrence, development, and migration of osteosarcoma. MATERIAL AND METHODS Somatic mutation screening was performed using the whole-exome sequencing of osteosarcoma samples, and the distribution of mutations was demonstrated by Circos diagrams. Metascape was used to analyze the GO and KEGG signal pathway enrichment of the genes harboring protein coding alterations, and GeneMANIA was used to analyze the interaction of mutated genes. Read More

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http://dx.doi.org/10.12659/MSM.920826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7106971PMC

Frequency of Pathogenic Germline Variants in Cancer-Susceptibility Genes in Patients With Osteosarcoma.

JAMA Oncol 2020 Mar 19. Epub 2020 Mar 19.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.

Importance: Osteosarcoma, the most common malignant bone tumor in children and adolescents, occurs in a high number of cancer predisposition syndromes that are defined by highly penetrant germline mutations. The germline genetic susceptibility to osteosarcoma outside of familial cancer syndromes remains unclear.

Objective: To investigate the germline genetic architecture of 1244 patients with osteosarcoma. Read More

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http://dx.doi.org/10.1001/jamaoncol.2020.0197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082769PMC

Germline variants underlie a subset of paediatric osteosarcoma.

J Med Genet 2020 Mar 16. Epub 2020 Mar 16.

Institute for Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.

Background: Although considerable effort has been put into decoding of the osteosarcoma genome, very little is known about germline mutations that underlie this primary malignant tumour of bone.

Methods And Results: We followed here a coincidental finding in a multiple endocrine neoplasia family in which a 32-year-old patient carrying a germline pathogenic mutation developed an osteosarcoma 2 years after the resection of a medullary thyroid carcinoma. Sequencing analysis of additional 336 patients with osteosarcoma led to the identification of germline activating mutations in the proto-oncogene in three cases and somatic amplifications of the gene locus in five matched tumours (4%, n=5/124 tumours). Read More

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http://dx.doi.org/10.1136/jmedgenet-2019-106734DOI Listing

MAPK7 variants related to prognosis and chemotherapy response in osteosarcoma.

Ann Diagn Pathol 2020 Feb 19;46:151482. Epub 2020 Feb 19.

Pediatric Oncology Institute (GRAACC), Federal University of São Paulo, Department of Pediatrics, São Paulo, SP, Brazil; Federal University of São Paulo, Department of Morphology and Genetics, São Paulo, SP, Brazil; Federal University of São Paulo, Department of Clinical and Experimental Oncology, São Paulo, SP, Brazil. Electronic address:

Osteosarcoma (OS) is a class of cancer originating from the bone, affecting mainly children and young adults. Our previous study showed that MAPK7 gene overexpression was significantly associated with tumor progression, poor treatment response, and worse overall survival, suggesting that MAPK7 could play an important role in OS tumorigenesis. We have investigated if MAPK7 overexpression was a result of any genomic changes in OS tumor specimens. Read More

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http://dx.doi.org/10.1016/j.anndiagpath.2020.151482DOI Listing
February 2020

[Expression of H3.3 G34W mutant-specific antibody in giant cell tumors of bone and its diagnostic value].

Zhonghua Bing Li Xue Za Zhi 2020 Feb;49(2):116-121

Department of Pathology, Medicine School of Nanjing University/Nanjing Jinling Hospital, Nanjing 210002, China.

To investigate the expression of H3.3 G34W mutant-specific antibody in giant cell tumors of bone (GCTB), and its value in the diagnosis of GCTB. Immunohistochemical (IHC) EnVision method was used to detect the expression of H3. Read More

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http://dx.doi.org/10.3760/cma.j.issn.0529-5807.2020.02.003DOI Listing
February 2020

[Malignant round cell tumors : The Ewing sarcoma and beyond].

Pathologe 2020 Mar;41(2):116-122

Institut für Pathologie, Univ.-Klinikum Magdeburg A.ö.R., Medizinische Fakultät, Otto-von-Guericke-Universität Magdeburg, Leipziger Straße 44, 39120, Magdeburg, Deutschland.

Ewing sarcomas are highly malignant tumors that are mainly found in children and adolescents. In addition to early clinical diagnosis, correct histopathological and molecular genetic classification is the most important step. Although EWSR1-FLI1 fusion is by far the most common detectable change, there are also other representatives of the Ewing sarcoma family that cannot be distinguished histopathologically and immunohistochemically from classical Ewing sarcomas and that have different molecular genetic profiles. Read More

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http://dx.doi.org/10.1007/s00292-020-00759-yDOI Listing

Functional variant of IL33 is associated with survival of osteosarcoma patients.

J Bone Oncol 2020 Feb 2;20:100270. Epub 2019 Dec 2.

Department of Orthopedic Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Zhongshan Road 321, Nanjing 210008, China.

Objectives: Previous genome-wide association study showed that loci were associated with overall survival in patients with osteosarcoma (OS). We performed a replication study to explore whether variants of are associated with the survival of OS patients and to further verify their functional role in the gene expression.

Methods: A total of 216 patients with OS were enrolled. Read More

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http://dx.doi.org/10.1016/j.jbo.2019.100270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931128PMC
February 2020

Enrichment of heterozygous germline loss-of-function variants in pediatric osteosarcoma.

Cold Spring Harb Mol Case Stud 2019 10 23;5(5). Epub 2019 Oct 23.

Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

Patients harboring germline pathogenic biallelic variants in genes involved in the recognition and repair of DNA damage are known to have a substantially increased cancer risk. Emerging evidence suggests that individuals harboring heterozygous variants in these same genes may also be at heightened, albeit lesser, risk for cancer. Herein, we sought to determine whether heterozygous variants in , the gene encoding an essential DNA helicase that is defective in children with the autosomal recessive cancer-predisposing condition Rothmund-Thomson syndrome (RTS), are associated with increased risk for childhood cancer. Read More

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http://dx.doi.org/10.1101/mcs.a004218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6824257PMC
October 2019
3 Reads

Ewing sarcoma with myxoid stroma: Case report of an unusual histological variant.

Pathol Res Pract 2019 Dec 24;215(12):152665. Epub 2019 Sep 24.

Department of Pathology, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, 251 East Huron St, Feinberg 7-342A, Chicago, IL 60611, United States.

We describe the case of a Ewing sarcoma with prominent myxoid stroma of the temporal bone in a 26-year-old female. Histologically, the tumor exhibited a fascicular growth pattern of round to spindled cells with a minimal amount of pale eosinophilic to clear cytoplasm and oval or spindled nuclei with finely dispersed chromatin and small nucleoli. Myxoid changes were prominent (>50%), with reticular or pseudoacinar growth of the loosely cohesive cells. Read More

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http://dx.doi.org/10.1016/j.prp.2019.152665DOI Listing
December 2019

Osteosarcoma without prior retinoblastoma related to RB1 low-penetrance germline pathogenic variants: A novel type of RB1-related hereditary predisposition syndrome?

Mol Genet Genomic Med 2019 12 30;7(12):e913. Epub 2019 Sep 30.

Medical Genetics Department, CHU Montpellier, Univ Montpellier, Montpellier, France.

Background: Retinoblastoma (Rb) is a rare intraocular malignant tumor in children with high overall survival. Predisposition to Rb is linked to RB1 germline mutations with high penetrance, but rare RB1 low-penetrance variants are also known. Rb survivors are at risk of second primary malignancies (SPMs), mostly osteosarcoma and soft-tissue sarcoma. Read More

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http://dx.doi.org/10.1002/mgg3.913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900371PMC
December 2019
2 Reads

Common genetic variation and risk of osteosarcoma in a multi-ethnic pediatric and adolescent population.

Bone 2020 Jan 13;130:115070. Epub 2019 Sep 13.

Department of Epidemiology and Biostatistics, University of California, San Francisco, United States; Duke Cancer Institute, Duke University, United States; Department of Neurosurgery, Duke University, United States. Electronic address:

Osteosarcoma, a malignant primary bone tumor most commonly diagnosed in children and adolescents, has a poorly understood genetic etiology. Genome-wide association studies (GWAS) and candidate-gene analyses have identified putative risk variants in subjects of European ancestry. However, despite higher incidence among African-American and Hispanic children, little is known regarding common heritable variation that contributes to osteosarcoma incidence and clinical presentation across racial/ethnic groups. Read More

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http://dx.doi.org/10.1016/j.bone.2019.115070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885126PMC
January 2020
3 Reads

Newly identified LMO3-BORCS5 fusion oncogene in Ewing sarcoma at relapse is a driver of tumor progression.

Oncogene 2019 11 5;38(47):7200-7215. Epub 2019 Sep 5.

Laboratoire de Vectorologie et Thérapeutiques Anticancéreuses, Université Paris-Sud 11, CNRS UMR 8203, Gustave Roussy Cancer Center, 94805, Villejuif, France.

Recently, we detected a new fusion transcript LMO3-BORCS5 in a patient with Ewing sarcoma within a cohort of relapsed pediatric cancers. LMO3-BORCS5 was as highly expressed as the characteristic fusion oncogene EWS/FLI1. However, the expression level of LMO3-BORCS5 at diagnosis was very low. Read More

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http://dx.doi.org/10.1038/s41388-019-0914-3DOI Listing
November 2019
2 Reads

Chondrosarcoma as inaugural manifestation of monostotic Paget's disease of Bone.

Acta Reumatol Port 2019 Apr-Jun;44(2):163-164

Centro Hospitalar São João.

Sarcomatous degeneration is one of the serious and rare complications of Paget's disease of bone. Osteosarcoma is the most common secondary tumour, while other variants such as chondrosarcoma are extremely uncommon. We describe a unique case of Paget's chondrosarcoma of the pelvis in an elderly female patient, with no previous established diagnosis of osteitis deformans. Read More

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February 2020
2 Reads

Integrative genomic analysis of matched primary and metastatic pediatric osteosarcoma.

J Pathol 2019 11 28;249(3):319-331. Epub 2019 Aug 28.

Department of Molecular Oncology, British Columbia Cancer Agency, Vancouver, Canada.

Despite being the most common childhood bone tumor, the genomic characterization of osteosarcoma remains incomplete. In particular, very few osteosarcoma metastases have been sequenced to date, critical to better understand mechanisms of progression and evolution in this tumor. We performed an integrated whole genome and exome sequencing analysis of paired primary and metastatic pediatric osteosarcoma specimens to identify recurrent genomic alterations. Read More

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http://dx.doi.org/10.1002/path.5319DOI Listing
November 2019
6 Reads

Separate domains of G3BP promote efficient clustering of alphavirus replication complexes and recruitment of the translation initiation machinery.

PLoS Pathog 2019 06 14;15(6):e1007842. Epub 2019 Jun 14.

Department of Microbiology, Tumor and Cell Biology, Biomedicum, Karolinska Institutet, Stockholm, Sweden.

G3BP-1 and -2 (hereafter referred to as G3BP) are multifunctional RNA-binding proteins involved in stress granule (SG) assembly. Viruses from diverse families target G3BP for recruitment to replication or transcription complexes in order to block SG assembly but also to acquire pro-viral effects via other unknown functions of G3BP. The Old World alphaviruses, including Semliki Forest virus (SFV) and chikungunya virus (CHIKV) recruit G3BP into viral replication complexes, via an interaction between FGDF motifs in the C-terminus of the viral non-structural protein 3 (nsP3) and the NTF2-like domain of G3BP. Read More

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http://dx.doi.org/10.1371/journal.ppat.1007842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594655PMC
June 2019
4 Reads

Functional testing of thousands of osteoarthritis-associated variants for regulatory activity.

Nat Commun 2019 06 4;10(1):2434. Epub 2019 Jun 4.

Department of Genome Sciences, University of Washington, Seattle, WA, 98195, USA.

To date, genome-wide association studies have implicated at least 35 loci in osteoarthritis but, due to linkage disequilibrium, the specific variants underlying these associations and the mechanisms by which they contribute to disease risk have yet to be pinpointed. Here, we functionally test 1,605 single nucleotide variants associated with osteoarthritis for regulatory activity using a massively parallel reporter assay. We identify six single nucleotide polymorphisms (SNPs) with differential regulatory activity between the major and minor alleles. Read More

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http://dx.doi.org/10.1038/s41467-019-10439-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547687PMC
June 2019
2 Reads

PTPRD copy number variants and Ewing's sarcoma: Strengthening the association and therapeutic implications.

Cancer Genet 2019 06 26;235-236:28-30. Epub 2019 Mar 26.

Department of Medical Genetics, BC Women's Hospital, Vancouver, British Columbia, Canada. Electronic address:

Ewing sarcoma (ES), a common pediatric primary bone neoplasm, has a well-defined genomic landscape with various predisposing genomic elements including TP53, PMS2 and RET. Additionally, germline and somatic variants in protein tyrosine phosphatase delta (PTPRD), a tumor suppressor gene, have been identified in a limited number of ES patients. Here we present an ES patient, remarkable in terms of his young age and extent at presentation, found to have a PTPRD CNV. Read More

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http://dx.doi.org/10.1016/j.cancergen.2019.03.004DOI 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466653PMC
April 2019
5 Reads

Relationship of common variants in Interleukin 33 gene with susceptibility and prognosis of osteosarcoma in Han Chinese population.

J Cancer 2019 29;10(5):1138-1144. Epub 2019 Jan 29.

Department of Joint Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.

Osteosarcoma (OS) is one of the most common malignant bone tumors. Many previous studies have indicated that OS is a complex disease and that its development may be affected by multiple genetic factors, which may contribute to its carcinogenesis. The aim of the present study was to evaluate the relationship of with susceptibility and prognosis of OS in Han Chinese individuals. Read More

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http://dx.doi.org/10.7150/jca.29086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400670PMC
January 2019
6 Reads

Primary paediatric epidural sarcomas: molecular exploration of three cases.

BMC Cancer 2019 Feb 28;19(1):182. Epub 2019 Feb 28.

Neurosurgical Service, KK Women's and Children's Hospital, Singapore, Singapore.

Background: Primary paediatric epidural sarcomas are extremely rare. Overall, there remains a paucity of knowledge in paediatric epidural sarcomas owing to the infrequent number of cases. The Archer FusionPlex Sarcoma Kit (ArcherDX, Inc) is a next-generation sequencing assay that has been reported to be a useful technique to detect recurrent fusion in sarcomas. Read More

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https://bmccancer.biomedcentral.com/articles/10.1186/s12885-
Publisher Site
http://dx.doi.org/10.1186/s12885-019-5368-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394101PMC
February 2019
33 Reads
3.362 Impact Factor

The relationship between metastatic potential and in vitro mechanical properties of osteosarcoma cells.

Mol Biol Cell 2019 03 20;30(7):887-898. Epub 2019 Feb 20.

Biomechanics Laboratory, University Hospital Balgrist, University of Zürich, 8008 Zürich, Switzerland.

Osteosarcoma is the most frequent primary tumor of bone and is characterized by its high tendency to metastasize in lungs. Although treatment in cases of early diagnosis results in a 5-yr survival rate of nearly 60%, the prognosis for patients with secondary lesions at diagnosis is poor, and their 5-yr survival rate remains below 30%. In the present work, we have used a number of analytical methods to investigate the impact of increased metastatic potential on the biophysical properties and force generation of osteosarcoma cells. Read More

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http://dx.doi.org/10.1091/mbc.E18-08-0545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589788PMC
March 2019
11 Reads
4.466 Impact Factor

A semiautomated whole-exome sequencing workflow leads to increased diagnostic yield and identification of novel candidate variants.

Cold Spring Harb Mol Case Stud 2019 04 1;5(2). Epub 2019 Apr 1.

Center for Personalized Medicine, Department of Pathology and Laboratory Medicine, Children's Hospital Los Angeles, Los Angeles, California 90027, USA.

Advancing the clinical utility of whole-exome sequencing (WES) for patients with suspected genetic disorders is largely driven by bioinformatics approaches that streamline data processing and analysis. Herein, we describe our experience with implementing a semiautomated and phenotype-driven WES diagnostic workflow, incorporating both the DRAGEN pipeline and the Exomiser variant prioritization tool, at an academic children's hospital with an ethnically diverse pediatric patient population. We achieved a 41% molecular diagnostic rate for 66 duo-, quad-, or trio-WES cases, and 28% for 40 singleton-WES cases. Read More

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http://dx.doi.org/10.1101/mcs.a003756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6549575PMC
April 2019
6 Reads

Integration of genomic copy number variations and chemotherapy-response biomarkers in pediatric sarcoma.

BMC Med Genomics 2019 01 31;12(Suppl 1):23. Epub 2019 Jan 31.

Herman B Wells Center for Pediatric Research, Department of Pediatrics, School of Medicine, Indiana University, Indianapolis, IN, 46202, USA.

Background: While most pediatric sarcomas respond to front-line therapy, some bone sarcomas do not show radiographic response like soft-tissue sarcomas (rhabdomyosarccomas) but do show 90% necrosis. Though, new therapies are urgently needed to improve survival and quality of life in pediatric patients with sarcomas. Complex chromosomal aberrations such as amplifications and deletions of DNA sequences are frequently observed in pediatric sarcomas. Read More

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http://dx.doi.org/10.1186/s12920-018-0456-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6357363PMC
January 2019
9 Reads
2.873 Impact Factor

Paget's Disease of Bone.

Calcif Tissue Int 2019 05 23;104(5):483-500. Epub 2019 Jan 23.

Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy.

Paget's disease of bone (PDB) is a chronic and focal bone disorder, characterized by increased osteoclast-mediated bone resorption and a subsequent compensatory increase in bone formation, resulting in a disorganized mosaic of woven and lamellar bone at one or more affected skeletal sites. As a result, bone pain, noticeable deformities, arthritis at adjacent joints, and fractures can occur. In a small proportion of cases neoplastic degeneration in osteosarcoma, or, less frequently, giant cell tumor has been also described at PDB sites. Read More

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http://dx.doi.org/10.1007/s00223-019-00522-3DOI Listing
May 2019
26 Reads

The Clonal Evolution of Metastatic Osteosarcoma as Shaped by Cisplatin Treatment.

Mol Cancer Res 2019 04 16;17(4):895-906. Epub 2019 Jan 16.

Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee.

To investigate the genomic evolution of metastatic pediatric osteosarcoma, we performed whole-genome and targeted deep sequencing on 14 osteosarcoma metastases and two primary tumors from four patients (two to eight samples per patient). All four patients harbored ancestral (truncal) somatic variants resulting in inactivation and cell-cycle aberrations, followed by divergence into relapse-specific lineages exhibiting a cisplatin-induced mutation signature. In three of the four patients, the cisplatin signature accounted for >40% of mutations detected in the metastatic samples. Read More

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http://mcr.aacrjournals.org/lookup/doi/10.1158/1541-7786.MCR
Publisher Site
http://dx.doi.org/10.1158/1541-7786.MCR-18-0620DOI Listing
April 2019
42 Reads

Risk stratification by somatic mutation burden in Ewing sarcoma.

Cancer 2019 04 2;125(8):1357-1364. Epub 2019 Jan 2.

Harvard Medical School, Boston, Massachusetts.

Background: Up to one-third of patients with localized Ewing sarcoma (ES) develop recurrent disease, but current biomarkers do not accurately identify this high-risk group. Therefore, the objective of this study was to determine the utility of mutational burden in predicting outcomes in patients with localized ES.

Methods: Clinical and genomic data from 99 patients with ES, of whom 63 had localized disease at diagnosis, were obtained from the cBioPortal for Cancer Genomics. Read More

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http://dx.doi.org/10.1002/cncr.31919DOI Listing
April 2019
3 Reads
4.889 Impact Factor

The Limb beyond Salvage: A Case Report on Two Cases of Fibroblastic Variants of Osteosarcoma.

J Orthop Case Rep 2019 ;9(4):96-100

Department of Surgery, School of Medicine and Health Science of the University for Development Studies and the Tamale Teaching Hospital, Ghana, West Africa.

Introduction: Management outcome of osteosarcoma as a primary bone malignancy is challenged in Ghana by many factors. We presented two male patients; aged 18 and 14 years, respectively, who were referred to the Tamale Teaching Hospital with advanced right knee tumors. Both patients had above knee amputation as part of treatment. Read More

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http://dx.doi.org/10.13107/jocr.2019.v09.i04.1498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7210912PMC
January 2019

MTHFR variant is associated with high-dose methotrexate-induced toxicity in the Chinese osteosarcoma patients.

J Bone Oncol 2018 Nov 1;13:143-147. Epub 2018 Nov 1.

Department of Orthopedic Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Zhongshan Road 321, Nanjing 210008, China.

Background: The role of Methylene tetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in the efficacy and toxicity of MTX-based therapy remains uncertain. Our purpose was to clarify whether these two polymorphisms are associated with the outcome of chemotherapy in a cohort of Chinese osteosarcoma (OS) patients treated by high-dose MTX.

Methods: 109 OS patients who had sequentially received high-dose MTX therapy were included in this study. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22121374183025
Publisher Site
http://dx.doi.org/10.1016/j.jbo.2018.10.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303521PMC
November 2018
28 Reads

Variants in the 14q32 miRNA cluster are associated with osteosarcoma risk in the Spanish population.

Sci Rep 2018 10 18;8(1):15414. Epub 2018 Oct 18.

Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of Medicine and Nursery, UPV/EHU, Leioa, Spain.

Association studies in osteosarcoma risk found significant results in intergenic regions, suggesting that regions which do not codify for proteins could play an important role. The deregulation of microRNAs (miRNAs) has been already associated with osteosarcoma. Consequently, genetic variants affecting miRNA function could be associated with risk. Read More

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http://www.nature.com/articles/s41598-018-33712-4
Publisher Site
http://dx.doi.org/10.1038/s41598-018-33712-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194014PMC
October 2018
30 Reads

Genetic determinants of childhood and adult height associated with osteosarcoma risk.

Cancer 2018 09 12;124(18):3742-3752. Epub 2018 Oct 12.

Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, California.

Background: Although increased height has been associated with osteosarcoma risk in previous epidemiologic studies, to the authors' knowledge the relative contribution of stature during different developmental timepoints remains unclear. Furthermore, the question of how genetic determinants of height impact osteosarcoma etiology remains unexplored. Genetic variants associated with stature in previous genome-wide association studies may be biomarkers of osteosarcoma risk. Read More

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http://doi.wiley.com/10.1002/cncr.31645
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http://dx.doi.org/10.1002/cncr.31645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214707PMC
September 2018
11 Reads
4.890 Impact Factor

Systematic meta-analysis of genetic variants associated with osteosarcoma susceptibility.

Medicine (Baltimore) 2018 Sep;97(38):e12525

Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

Background: In the past decade, accumulated evidence has suggested that genetic variation is related to the pathogenesis of osteosarcoma. Although there are a large number of studies on the association between genetic variation and osteosarcoma, their results are inconsistent. To clarify these findings, we performed a systematic meta-analysis using allelic contrasts for each gene-specific single nucleotide variants with all available data in the field of osteosarcoma. Read More

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http://dx.doi.org/10.1097/MD.0000000000012525DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160068PMC
September 2018
4 Reads

Variants of FasL and ABCC5 are predictive of outcome after chemotherapy-based treatment in osteosarcoma.

J Bone Oncol 2018 Sep 3;12:44-48. Epub 2018 May 3.

Department of Orthopedic Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Zhongshan Road 321, Nanjing 210008, China.

Objectives: Previous pharmacogenetics studies showed that genetic variants could be indicative of the response to chemotherapy. We aimed to investigate whether variants of FasL, MSH2, ABCC5, CASP3 and CYP3A4 are associated with the outcome after chemotherapy-based treatment in osteosarcoma.

Methods: 132 osteosarcoma patients who had completed the neoadjuvant chemotherapy in our center were included. Read More

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http://dx.doi.org/10.1016/j.jbo.2018.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066469PMC
September 2018
22 Reads

Two HLA Class II Gene Variants Are Independently Associated with Pediatric Osteosarcoma Risk.

Cancer Epidemiol Biomarkers Prev 2018 10 23;27(10):1151-1158. Epub 2018 Jul 23.

Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.

The genetic etiology of osteosarcoma remains poorly understood despite the publication of a genome-wide association study. Association between HLA genetic variants and risk of several cancers has been observed, but HLA variation is not well captured by standard SNP arrays. We genotyped 207 Californian pediatric osteosarcoma cases and 696 controls of European ancestry using a custom genome-wide array supplemented with approximately 6,000 additional probes across the MHC region. Read More

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http://dx.doi.org/10.1158/1055-9965.EPI-18-0306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6170682PMC
October 2018
54 Reads

Detection of Somatic Structural Variants Enables Quantification and Characterization of Circulating Tumor DNA in Children With Solid Tumors.

JCO Precis Oncol 2018 5;2018. Epub 2018 Jul 5.

Dana-Farber Cancer Institute, Boston.

Objective: Liquid biopsies are being rapidly used in adult cancers as new biomarkers of disease. Circulating tumor DNA (ctDNA) levels have been reported to be proportional to disease burden, correlate with treatment response, and predict relapse. However, little is known about how frequently ctDNA is detectable in pediatric patients with solid tumors. Read More

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6049092PMC
http://dx.doi.org/10.1200/PO.17.00285DOI Listing
July 2018
32 Reads

Glucocorticoid Receptor Mutations and Hypersensitivity to Endogenous and Exogenous Glucocorticoids.

J Clin Endocrinol Metab 2018 10;103(10):3630-3639

National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina.

Background: The glucocorticoid receptor (GR) consists of two alternatively spliced isoforms: GRα, which activates gene transcription, and GRβ, a dominant-negative receptor. Theoretically, inactivating variants of GRβ could result in glucocorticoid hypersensitivity.

Design: A 46-year-old woman presented for evaluation of adrenal insufficiency prompted by low plasma cortisol levels and multiple unexplained symptoms but without clinical evidence of glucocorticoid insufficiency. Read More

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http://dx.doi.org/10.1210/jc.2018-00352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179182PMC
October 2018
37 Reads

Possible roles of genetic variations in chemotherapy related cardiotoxicity in pediatric acute lymphoblastic leukemia and osteosarcoma.

BMC Cancer 2018 Jul 3;18(1):704. Epub 2018 Jul 3.

Department of Genetics, Cell- and Immunobiology, Semmelweis University, 1089 Nagyvárad tér 4., 6 em, Budapest, 611, Hungary.

Background: The treatment of acute lymphoblastic leukemia (ALL) and osteosarcoma (OSC) is very effective: the vast majority of patients recover and survive for decades. However, they still need to face serious adverse effects of chemotherapy. One of these is cardiotoxicity which may lead to progressive heart failure in the long term. Read More

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https://bmccancer.biomedcentral.com/articles/10.1186/s12885-
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http://dx.doi.org/10.1186/s12885-018-4629-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6029426PMC
July 2018
34 Reads

A subregion-based burden test for simultaneous identification of susceptibility loci and subregions within.

Genet Epidemiol 2018 10 22;42(7):673-683. Epub 2018 Jun 22.

Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland.

In rare variant association studies, aggregating rare and/or low frequency variants, may increase statistical power for detection of the underlying susceptibility gene or region. However, it is unclear which variants, or class of them, in a gene contribute most to the association. We proposed a subregion-based burden test (REBET) to simultaneously select susceptibility genes and identify important underlying subregions. Read More

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http://dx.doi.org/10.1002/gepi.22134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185783PMC
October 2018
33 Reads

The Alzheimer's disease-associated TREM2 gene is regulated by p53 tumor suppressor protein.

Neurosci Lett 2018 08 26;681:62-67. Epub 2018 May 26.

Center for Translational Research and Molecular Biology of Cancer, Maria Skłodowska-Curie Institute-Oncology Center, Gliwice Branch, 44-101 Gliwice, Poland. Electronic address:

TREM2 mutations evoke neurodegenerative disorders, and recently genetic variants of this gene were correlated to increased risk of Alzheimer's disease. The signaling cascade originating from the TREM2 membrane receptor includes its binding partner TYROBP, BLNK adapter protein, and SYK kinase, which can be activated by p53. Moreover, in silico identification of a putative p53 response element (RE) at the TREM2 promoter led us to hypothesize that TREM2 and other pathway elements may be regulated in p53-dependent manner. Read More

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http://dx.doi.org/10.1016/j.neulet.2018.05.037DOI Listing
August 2018
12 Reads

Fibrous Dysplasia: Clinicopathologic Presentation of 36 Cases.

Turk Patoloji Derg 2018 ;34(3):234-241

Department of Surgical Pathology, Uludag University Faculty of Medicine , BURSA, TURKEY.

Objective: Fibrous dysplasia is a slowly progressing bone lesion resulting from displacement of the normal medullary bone with abnormal fibroosseous tissue. The aim of this study was to assess the similarities and differences of our cases in relation to published reports.

Material And Method: In this study, the archives of the Uludag University Medical Faculty Department of Pathology were screened for fibrous dysplasia cases between 2004 and 2016. Read More

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http://dx.doi.org/10.5146/tjpath.2018.01428DOI Listing
December 2018
11 Reads

Does ATRX germline variation predispose to osteosarcoma? Three additional cases of osteosarcoma in two ATR-X syndrome patients.

Eur J Hum Genet 2018 08 30;26(8):1217-1221. Epub 2018 Apr 30.

Unité INSERMU830, Institut Curie, Paris, France.

Osteosarcoma is the most common malignant bone tumor in adolescents and young adults. Most osteosarcomas are sporadic but the risk of osteosarcoma is also increased by germline variants in TP53, RB1 and RECQL4 genes. ATRX germline variations are responsible for the rare genetic disorder X-linked alpha-thalassemia mental retardation (ATR-X) syndrome characterized by severe developmental delay and alpha-thalassemia but no obvious increased risk of cancer. Read More

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http://dx.doi.org/10.1038/s41431-018-0147-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057977PMC
August 2018
63 Reads

Incorporating Si N into PEEK to Produce Antibacterial, Osteocondutive, and Radiolucent Spinal Implants.

Macromol Biosci 2018 06 24;18(6):e1800033. Epub 2018 Apr 24.

Department of Immunology, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto, 602-8566, Japan.

Polyetheretherketone (PEEK) is a popular polymeric biomaterial which is primarily used as an intervertebral spacer in spinal fusion surgery; but it is developed for trauma, prosthodontics, maxillofacial, and cranial implants. It has the purported advantages of an elastic modulus which is similar to native bone and it can be easily formed into custom 3D shapes. Nevertheless, PEEK's disadvantages include its poor antibacterial resistance, lack of bioactivity, and radiographic transparency. Read More

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http://dx.doi.org/10.1002/mabi.201800033DOI Listing
June 2018
4 Reads