Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0279530 (bone cancer)
 1,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We used the nation-wide Swedish Family-Cancer Database to analyze the risk for bone cancer in offspring by parental cancers and in siblings of bone cancer probands. Additionally, the risk of second cancer following childhood bone cancer was investigated. In offspring, 1,190 bone cancers were diagnosed between years 1958 and 1996. Groups of offspring were compared by calculating standardized incidence ratios (SIRs) for bone cancer. Most bone cancer cases occurred sporadically. Parental breast (SIR 1.7) and prostate (SIR 1.7) cancers were associated with early-onset (<25 years) osteosarcoma in offspring, probably due to Li-Fraumeni syndrome. Giant cell sarcoma was increased by parental breast cancer (SIR 2.9), and early-onset chondrosarcoma by parental kidney cancers (SIR 6.8). Bone cancers conveyed a high risk of second bone and connective tissue cancer.
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PMID:Parental cancer as a risk factor for bone cancer: a nation-wide study from Sweden. 1180 47

We used the nation-wide Swedish Family-Cancer Database to examine the familial risks of histology-specific bone cancers in offspring by parental or sibling probands. Adjusted standardised incidence ratios (SIRs) were used to measure the risk. Among the 1327 offspring bone cancers, only two parent-offspring pairs and one sibling pair were noted with concordant bone cancer but the SIRs were not significant. Significant associations were observed in specific histological types or specific age groups, some of which may be chance findings arising from multiple comparisons. However, the risk of early-onset (< 25 years) osteosarcoma in offspring was significantly increased when mothers presented with breast cancer (1.7) and melanoma (2.9), suggesting that Li-Fraumeni syndrome could partly explain this familial aggregation. Other associations, such as childhood osteosarcoma with parental liver cancer, Ewing's sarcoma with kidney cancer and giant cell sarcoma with maternal breast cancer, were novel findings and may be related to other familial diseases.
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PMID:Familial risk for histology-specific bone cancers: an updated study in Sweden. 1685 7

Osteosarcoma is the most common form of bone cancer. Pivotal insight into the genes involved in human osteosarcoma has been provided by the study of rare familial cancer predisposition syndromes. Three kindreds stand out as predisposing to the development of osteosarcoma: Li-Fraumeni syndrome, familial retinoblastoma and RecQ helicase disorders, which include Rothmund-Thomson Syndrome in particular. These disorders have highlighted the important roles of P53 and RB respectively, in the development of osteosarcoma. The association of OS with RECQL4 mutations is apparent but the relevance of this to OS is uncertain as mutations in RECQL4 are not found in sporadic OS. Application of the knowledge or mutations of P53 and RB in familial and sporadic OS has enabled the development of tractable, highly penetrant murine models of OS. These models share many of the cardinal features associated with human osteosarcoma including, importantly, a high incidence of spontaneous metastasis. The recent development of these models has been a significant advance for efforts to improve our understanding of the genetics of human OS and, more critically, to provide a high-throughput genetically modifiable platform for preclinical evaluation of new therapeutics.
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PMID:Genetically engineered mouse models and human osteosarcoma. 2303 72

Childhood neoplasms are relatively rare and represent only about 1- 2% of the total incidence of neoplasms in United States. Concurrent episode of childhood cancer is uncommon and usually related to a cancer genetic syndrome. Li Fraumeni Syndrome refers to an autosomal dominant condition that is manifested by the development of certain cancers in early childhood and an increased lifetime risk for developing multiple primary cancers including sarcoma, breast cancer, leukemia, bone cancer, and others. We report a case of a 21-month-old girl who was found to have orbital embryonal rhabdomyosarcoma and adrenocortical tumor concurrently.
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PMID:A concurrent episode of two neoplasms in a toddler-age child. 2476 85

Osteosarcoma (OS) is the most frequent primary bone cancer in children and adolescents and the third most frequent in adults. Many inherited germline mutations are responsible for syndromes that predispose to osteosarcomas including Li Fraumeni syndrome, retinoblastoma syndrome, Werner syndrome, Bloom syndrome or Diamond-Blackfan anemia. TP53 is the most frequently altered gene in osteosarcoma. Among other genes mutated in more than 10% of OS cases, c-Myc plays a role in OS development and promotes cell invasion by activating MEK-ERK pathways. Several genomic studies showed frequent alterations in the RB gene in pediatric OS patients. Osteosarcoma driver mutations have been reported in NOTCH1, FOS, NF2, WIF1, BRCA2, APC, PTCH1 and PRKAR1A genes. Some miRNAs such as miR-21, -34a, -143, -148a, -195a, -199a-3p and -382 regulate the pathogenic activity of MAPK and PI3K/Akt-signaling pathways in osteosarcoma. CD133+ osteosarcoma cells have been shown to exhibit stem-like gene expression and can be tumor-initiating cells and play a role in metastasis and development of drug resistance. Although currently osteosarcoma treatment is based on adriamycin chemoregimens and surgery, there are several potential targeted therapies in development. First of all, activity and safety of cabozantinib in osteosarcoma were studied, as well as sorafenib and pazopanib. Finally, novel bifunctional molecules, of potential imaging and osteosarcoma targeting applications may be used in the future.
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PMID:Molecular Biology of Osteosarcoma. 3275 22

Osteosarcoma is the most common type of bone cancer. Osteosarcoma is commonly associated with TP53 inactivation (around 95% of cases) and RB1 inactivation (around 28% of cases). With the discovery of reprogramming factors to induce pluripotency even in terminally differentiated cells, induced pluripotent stem cells (iPSCs) have emerged as a promising disease model. iPSC-based disease modeling uniquely recapitulates disease phenotypes and can support discoveries into disease etiology and is used extensively today to study a variety of diseases, including cancers. This paper focuses on iPSC-based modeling of Li-Fraumeni syndrome (LFS), an autosomal dominant disorder commonly associated with TP53 mutation and high osteosarcoma incidence. As iPSCs are increasingly utilized as a platform for cancer modeling, the experimental approaches that we discuss here may serve as a guide for future studies.
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PMID:Modeling of osteosarcoma with induced pluripotent stem cells. 3302 33