Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cytogenetic analysis of a highly malignant osteosarcoma in a 17-year-old girl revealed extremely complex karyotypic changes with several different clonal numerical and structural chromosome aberrations. The composite karyotype was interpreted as 39-41,X,t(X;9)(q11;p24), -1,der(1), -4, -4, -5,i(7q),-8,del(8)(q21),t(10;19)(p13;q13),del(11)(p11p13), t(12;18)(q24;q12), -13,13q+,-14,14p+,-15,15q+,17p+,19q+,-21,+22,+3-6 mar.
 ...
PMID:Multiple cytogenetic abnormalities in a case of osteosarcoma. 346 46

A case of therapy-related AML with t(8;16)(p11;p13) 14 months following the end of anthracycline-containing chemotherapy for a nonmetastatic osteosarcoma of the left tibia is presented. The patient was successfully treated with intensive remission-induction chemotherapy. Subsequently, he underwent an uncomplicated allogeneic bone marrow transplantation from his HLA-identical brother and is at present alive and disease-free 10 months after diagnosis of the secondary AML.
 ...
PMID:Therapy-related acute myeloid leukemia with t(8;16)(p11;p13) following anthracycline-based therapy for nonmetastatic osteosarcoma. 766 38

Relatively few karyotypes have been reported from short-term cultures and/or direct harvests of osteosarcomas. We describe clonal aberrations in 17 high-grade osteosarcoma specimens and in one low-grade osteosarcoma. The high-grade osteosarcomas were karyotyped after direct harvest (four cases) or after short-term culture periods of < 1 week (13 cases). Three of these specimens, a primary osteosarcoma and two lung metastases, were from the same patient and shared a number of clonal aberrations. No consistent chromosome translocations were identified in the overall group of high-grade osteosarcomas, but potential nonrandom deletions involved 6q21-->qter, 9p21-->pter, chromosome 10, chromosome 13, 17p12-pter, and chromosome 20. Ring chromosomes were detected in three cases, and double-minute (dmin) chromosomes were detected in six. All high-grade osteosarcomas had numerous nonclonal chromosome aberrations superimposed on complex clonal events. The single low-grade osteosarcoma was characterized by a balanced, nonconstitutional, t(5;10) (p13;p14-15), together with an addition to the short arm of chromosome X. This is the first translocation reported in low-grade osteosarcoma, and the simplicity of the karyotype contrasts strikingly with those in the high-grade osteosarcomas.
 ...
PMID:Cytogenetic aberrations in osteosarcomas. Nonrandom deletions, rings, and double-minute chromosomes. 792 89

Chromosomal translocations resulting in chimaeric transcription factors underlie specific malignancies, but few authentic target genes regulated by these fusion proteins have been identified. Desmoplastic small round-cell tumour (DSRT) is a multiphenotypic primitive tumour characterized by massive reactive fibrosis surrounding nests of tumour cells. The t(11;22)(p13;q12) chromosomal translocation that defines DSRT produces a chimaeric protein containing the potential transactivation domain of the Ewing-sarcoma protein (EWS) fused to zinc fingers 2-4 of the Wilms tumour suppressor and transcriptional repressor WT1 (refs 2,3). By analogy with other EWS fusion products, the EWS-WT1 chimaera may encode a transcriptional activator whose target genes overlap with those repressed by WT1 (ref. 4). To characterize its functional properties, we generated osteosarcoma cell lines with tightly regulated inducible expression of EWS-WT1. Expression of EWS-WT1 induced the expression of endogenous platelet-derived growth factor-A (PDGFA), a potent secreted mitogen and chemoattractant whose promoter contains the many potential WT1-binding sites. Native PDGFA was not regulated by wild-type WT1, indicating a difference in target gene specificity between this tumour suppressor and its oncogenic derivative. PDGFA was expressed within tumour cells in primary DSRT specimens, but it was absent in Wilms tumours expressing WT1 and Ewing sarcomas with an EWS-Fli translocation. We conclude that the oncogenic fusion of EWS to WT1 in DSRT results in the induction of PDGFA, a potent fibroblast growth factor that contributes to the characteristic reactive fibrosis associated with this unique tumour.
 ...
PMID:The EWS-WT1 translocation product induces PDGFA in desmoplastic small round-cell tumour. 935 95

We describe five primary soft tissue tumors that had histologic features identical to intraosseous aneurysmal bone cyst. The tumors occurred in three females and two males, who ranged in age from 8 to 37 years (median 28 years). They arose in the deep soft tissue of the upper extremities, thigh, and groin region and typically presented as a rapidly growing mass; no involvement of the adjacent bones was identified. The tumors ranged in size from 2.5 to 9 cm (median 4 cm). Grossly, they were surrounded by a thin rim of bone and on sectioning had hemorrhagic cystic spaces delineated by fibrous septa. Histologically, the cystic spaces were filled with blood and the fibrous septa were composed of fibroblasts, osteoclast-type giant cells, and woven bone. Cytogenetic analysis of one tumor showed 46,XY,t(17;17)(p13;q12), a result similar to that which has been reported for intraosseous aneurysmal bone cyst. The differential diagnosis includes a variety of bone-forming and giant cell-containing tumors, the most important being extraskeletal osteosarcoma. Follow-up showed that four patients are free of disease 16 months to 10 years after surgery; one tumor regrew after incomplete initial excision, but the patient has been free of disease 16 months after a second operation. Soft tissue aneurysmal bone cyst is an uncommon benign tumor that can be treated by simple excision, and it should be distinguished from a variety of other reactive and neoplastic processes.
 ...
PMID:Soft tissue aneurysmal bone cyst: a clinicopathologic study of five cases. 1175 70

Little is known about the genomic alterations underlying osteosarcoma. We performed a genomewide high-resolution gene copy number analysis of 22 osteosarcoma samples using comparative genomic hybridization on a cDNA microarray that contained cDNA clones of about 13,000 genes. Nineteen of the 22 cases had amplifications that on average spanned more than 1 Mb and contained more than 10 genes. Numerous regions of gain and loss were identified, and their boundaries were defined at high resolution. Novel amplicons were found at 14q11, 17q25, and 22q11-q13. Earlier-known large amplified regions were detected at 12q11-q15, 8q24, 6p12-p13, and 17p11-p13 in 8, 6, 5, and 4 of the 22 samples, respectively. Amplification of 12q was observed more frequently (36% of the cases) than previously reported. Previously known small amplicons at 1p34-p36, 1q21, 19q13, and 21q22 were seen in at least three cases. Our results implicate TOM1L2 and CYP27B1 as having roles as novel targets for the 17p and 12q amplicons, respectively. Details (www.helsinki.fi/cmg) of the amplified genes in each amplicon provide valuable raw data for further in silico studies.
 ...
PMID:Gene amplifications in osteosarcoma-CGH microarray analysis. 1554 Jan 65

We examined 14 spindle cell tumours of the pleura that were sent to a Mesothelioma Panel for re-evaluation after a primary suspicion of mesothelioma. The clinical, histological, immunohistochemical and CGH findings were investigated. Final diagnoses were eight sarcomatoid mesotheliomas (SM) and six non-mesotheliomas: two pulmonary sarcomatoid carcinomas, an epithelioid hemangioendothelioma, a malignant solitary fibrous tumour, a malignant pleural smooth muscle tumour and an extraskeletal osteosarcoma. Seven of the eight SM and two of the other six tumours presented with unilateral pleural effusion, dyspnoea, and chest pain, which are characteristic clinical findings in malignant mesothelioma. No single antibody used in the immunohistochemistry separated SM from other tumour types. The most frequently observed chromosomal losses in SM were 4q, 4p11-p13/p15, 6q and 13. Losses of 4p11-p13/p15 and 4q occurred in combination in four out of five SM with detectable chromosomal changes, but neither was found in any of the other tumours. Gain or high-level amplification of 5p was also common in SM. According to our results and literature, losses at 4p, 4q and 9p and gain at 5p are the chromosomal changes that best differentiate SM from pleural sarcomas and lung carcinomas. CGH analysis may help distinguish a cytokeratin-positive SM from a sarcomatoid carcinoma. Similarly, in the case of a cytokeratin-negative tumour, CGH analysis may disclose chromosomal changes characteristic of sarcomas or mesotheliomas.
 ...
PMID:Spindle cell tumours of the pleura: a clinical, histological and comparative genomic hybridization analysis of 14 cases. 1617 May 37

The amplification or gain of the p-arm of chromosome 17 is common in sarcomas, suggesting its role in carcinogenesis. Here, we report the architectural structure and targets of 17p aberrations commonly shared by osteosarcoma (OS), leiomyosarcoma (LMS) and malignant fibrous histiocytoma (MFH) of soft tissue. Two low-grade and two high-grade soft tissue LMS, three OS, and two MFH samples were studied using fine-resolution oligonucleotide-based microarray comparative genomic hybridization. Eight of the nine samples showed a loss of 17pter-->p13, the locus of tumor suppressor TP53 preceding the amplified area 17p12-->p11.2. The size and detailed architecture of the amplified region of 17p differed between the studied sarcoma entities. OS and high-grade LMS showed similar complex patterns of discontinuous amplifications with regions of gain in between. MFH and low-grade LMS showed continuous regions of gains and amplifications. Precise boundaries of the lost or gained regions were determined, and in addition to the previously suggested targets of the region, ELAC and FLCN were amplified in all the sarcoma entities.
 ...
PMID:Loss of TP53 in sarcomas with 17p12 to approximately p11 gain. A fine-resolution oligonucleotide array comparative genomic hybridization study. 1731 53

We report a case of treatment-related acute myeloid leukemia (t-AML) in a 16-year-old male following treatment for osteosarcoma (OS). He had been treated with a protocol comprising neoadjuvant chemotherapy, definitive surgery with wide excision and adjuvant chemotherapy for OS. Four months after completion of the treatment, a routine hemogram showed hyperleukocytosis with 90% blasts. Bone marrow aspirate and a chromosomal analysis disclosed acute myeloid leukemia (AML), M5b with 46, XY, t(11;19)(q23;p13.3). The t-AML was characterized by early development (just 4 months after completion of chemotherapy for OS) and generalized leukemia cutis. The patient received an alkylating agent (ifosfamide) and DNA topoisomerase II-targeted drugs (etoposide and doxorubicin). In terms of latency, cytogenetics, and presentation, DNA topoisomerase II-targeted drug-related leukemia seemed likely for this patient. Clinically, his leukemia cutis had developed during a nadir in white blood cell count after the first induction of chemotherapy for AML. The rapid progression and its refractoriness to chemotherapy were poor prognostic signs.
 ...
PMID:Early development of acute myeloid leukemia following treatment of osteosarcoma: a case report and review of the literature. 1985 69