The Genetics of Osteosarcoma

Martin, Jeff W.; Squire, Jeremy A.; Zieleńska, Maria

doi:10.1155/2012/627254

Cited by 216 publications

(240 citation statements)

References 127 publications

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“…38,39 Although questions remain as to the molecular basis of osteosarcoma, patients frequently present with highgrade tumors seemingly of osteoblastic or fibroblastic origin. The miRNA signatures within osteosarcoma have been shown to associate with pathological features, whereas specific miRNAs can regulate tumor progression and metastasis 40 ( Figure 1b and Table 2).…”

Section: Mirna Expression Influences Growth and Progression Of Osteosmentioning

confidence: 99%

MicroRNAs as regulators of bone homeostasis and bone metastasis

Ell

Kang

2014

Bonekey Reports

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MicroRNAs (miRNAs) are short, endogenous RNAs that have essential roles in regulating gene expression through the disruption of target genes. The miRNA-induced suppression can occur through Argonaute-mediated cleavage of target mRNAs or by translational inhibition. System-wide studies have underscored the integral role that miRNAs play in regulating the expression of essential genes within bone marrow stromal cells. The miRNA expression has been shown to enhance or inhibit cell differentiation and activity, and elucidating miRNA targets within bone marrow cells has revealed novel regulations during normal bone development. Importantly, multiple studies have shown that miRNA misexpression mediates the progression of bone-related pathologies, including osteopetrosis and osteoporosis, as well as the development and progression of osteosarcoma. Furthermore, recent studies have detailed the capacity for miRNAs to influence bone metastasis from a number of primary carcinomas. Taken together, these findings reveal the significant clinical potential for miRNAs to regulate bone homeostasis, as well as to mediate bone-related pathologies.BoneKEy Reports 3, Article number: 549 (2014) | doi:10.1038/bonekey.2014.44 MiRNA Biogenesis and FunctionThe past decade has seen a torrent of novel research into the post-translational regulation of genes via microRNA-mediated suppression. The microRNAs (miRNAs) are a class of B22-nucleotide-long RNAs that repress gene expression through complementary binding to sites in the 3 0 -untranslated region (UTR) of target mRNAs. 1 Mature miRNAs are generated by the sequential cleavage of longer precursor transcripts, or pri-miRNAs, that are typically transcribed from intragenic or intergenic regions by RNA polymerase II. 2 The initial cleavage step, mediated by Drosha and the DGCR8 complex, occurs in the nucleus and produces a shortened (70-100 nucleotides) pre-miRNA hairpin. Pre-miRNAs are exported from the nucleus by Exportin 5, followed by a second cleavage by the ribonuclease Dicer that produces a double-stranded, B18-25-nucleotide-long mature miRNA. One miRNA strand will then combine with Argonaute (AGO2) proteins to produce an RNAinduced silencing complex, allowing for directed pairing with target mRNAs. 1

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Section: Mirna Expression Influences Growth and Progression Of Osteosmentioning

confidence: 99%

MicroRNAs as regulators of bone homeostasis and bone metastasis

Ell

Kang

2014

Bonekey Reports

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“…Osteosarcoma is a genetically complex, heterogeneous disease that occurs naturally in humans and dogs (1)(2)(3). In the past decade, the molecular basis of osteosarcoma has received significant attention, and a number of recurring chromosomal aberrations and changes in gene expression have been identified (1)(2)(3)(4)(5).…”

mentioning

confidence: 99%

“…In the past decade, the molecular basis of osteosarcoma has received significant attention, and a number of recurring chromosomal aberrations and changes in gene expression have been identified (1)(2)(3)(4)(5). However, these findings have not yet translated into significant improvements in disease prognosis or outcome (2, 6 -8), placing osteosarcoma among the "most wanted" for new and effective therapies (9).…”

mentioning

confidence: 99%

Aberrant Retinoblastoma (RB)-E2F Transcriptional Regulation Defines Molecular Phenotypes of Osteosarcoma

Scott

Sarver

Tomiyasu

et al. 2015

Journal of Biological Chemistry

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Background: Gene expression signatures define prognostically significant osteosarcoma phenotypes. Results: Deregulation of the RB-E2F pathway establishes more aggressive phenotype. Inhibitors of DNA and chromatin remodeling promote comparable transcriptional changes as genetic restoration of RB. Conclusion: Aberrant RB-E2F pathway alters epigenetic landscape and biological behavior of osteosarcoma. Significance: Epigenetic remodeling regulated by RB-E2F gives rise to patterns of gene expression that are associated with different biological behavior and progression of osteosarcoma.

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“…CIN can contribute to tumor initiation and progression through altering the expression of proto-oncogenes or tumor suppressor genes. The rate of gain or loss of entire chromosomes or sections is signiicant in the pathogenesis of osteosarcoma resulting in numerous aberrations and wide variability between cells and tumors [27].…”

Section: Chromosomal Abnormalitiesmentioning

confidence: 99%

Osteosarcomagenesis: Biology, Development, Metastasis, and Mechanisms of Pain

Smeester¹,

Moriarity²,

Beitz³

2017

Osteosarcoma - Biology, Behavior and Mechanisms

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Osteosarcoma is the most common primary cancer of the bone and third most common cancer in children and adolescents with approximately 900 new cases annually in the United States. A major facet of osteosarcoma is its high level of genomic instability, in particular chromosomal instability, which is the result of increased or decreased chromosome number in a cell. Furthermore, pain is the most common symptomatic feature of osteosarcoma that lacks efective therapy. Pain in osteosarcoma is relatively more complicated than many other painful conditions requiring a more thorough understanding of its etiology, pathobiology, and neurobiology to allow the development of beter therapies for reducing pain in osteosarcoma patients. Studies are underway to deine the diverse modalities of presentation, growth, development, metastases, and nociception in osteosarcoma. New data from human studies in combination with data from studies incorporating transgenic mouse models of osteosarcoma are providing valuable insights into the mechanisms underlying the development of both the tumor and the tumor-induced pain. These new data will undoubtedly lead to improved prognoses, as well as the development of novel therapeutics that will signiicantly decrease bone cancer pain.

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The Genetics of Osteosarcoma

Cited by 216 publications

References 127 publications

MicroRNAs as regulators of bone homeostasis and bone metastasis

MicroRNAs as regulators of bone homeostasis and bone metastasis

Aberrant Retinoblastoma (RB)-E2F Transcriptional Regulation Defines Molecular Phenotypes of Osteosarcoma

Osteosarcomagenesis: Biology, Development, Metastasis, and Mechanisms of Pain

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