Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sarcoma is a rare disease that always metastasizes to the lungs and bones. Myxoid liposarcoma (MLPS), in comparison with other sarcomas, has a distinct biological characteristic. Recent studies have suggested that MLPS expresses high levels of adipophilin and chemokine (C-X-C motif) receptor 4 (CXCR4), which are correlated with adipogenesis and metastasis. In addition, the Ewing sarcoma breakpoint region 1-DNA damage-inducible transcript 3 (EWSR1-DDIT3) fusion transcript, recently identified in MLPS, was shown to selectively repress the osteoblastic transcription in multipotent mesenchymal cells. The present study reported a rare case of MLPS with metastasis in fat-bearing areas, including the bones, epidural region, orbits and abdominal cavity, while the lungs were not involved. Bone metastasis was diagnosed by magnetic resonance imaging and proven by histology. However, bone scanning lacked sufficient sensitivity to detect the bone metastasis. Based on these findings, we hypothesized that molecular adipophilin and molecular CXCR4 may contribute to the fat-bearing area metastasis pattern. Furthermore, the EWSR1-DDIT3 fusion transcript may repress the osteoblastic activity in the bone metastases, ultimately resulting in a low detection rate by bone scans.
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PMID:Metastasis of myxoid liposarcoma to fat-bearing areas: A case report of unusual metastatic sites and a hypothesis. 2662 86

Sclerosing epithelioid fibrosarcoma (SEF) is an aggressive soft tissue sarcoma, characterized by a distinctive epithelioid phenotype in a densely sclerotic collagenous stroma, that shows frequent MUC4 immunoreactivity and recurrent gene fusions, often involving EWSR1 gene. A pathogenetic link with low-grade fibromyxoid sarcoma (LGFMS) has been suggested, due to cases with hybrid morphology as well as overlapping genetic signature. However, a small subset of SEF is negative for MUC4 and lacks the canonical EWSR1/FUS gene rearrangements. Triggered by the identification of recurrent YAP1-KMT2A gene fusions by RNA sequencing in 3 index cases of MUC4-negative, EWSR1/FUS fusion-negative SEF, we further investigated a cohort of 14 similar SEF cases (MUC4-negative, EWSR1/FUS fusion-negative) by fluorescence in situ hybridization (FISH), reverse transcription-polymerase chain reaction, and/or DNA-based massively parallel sequencing (MSK-IMPACT) for abnormalities in these genes. Three additional SEFs with KMT2A gene rearrangements and one additional case with YAP1 gene rearrangements were identified by FISH. In addition, one case with YAP1-KMT2A and one with KMT2A-YAP1 fusion were detected by reverse transcription-polymerase chain reaction and MSK-IMPACT, respectively. As a control group, 24 fibromyxoid spindle cell tumors, diagnosed or suspected as fusion-negative LGFMS, were also tested for YAP1 and KMT2A abnormalities by FISH, but none were positive. The YAP1/KMT2A-rearranged SEF group affected patients ranging from 10 to 86 years old (average and median: 45) of both sexes (4 females, 5 males). The tumors involved somatic soft tissues with a wide distribution, including extremities, trunk, neck, and dura. Histologically, the tumors showed variable cellularity, with monotonous ovoid to epithelioid tumor cells and hyalinized collagenous background typical of SEF. More than half of the cases showed infiltrative borders, within fat or skeletal muscle. No LGFMS component was identified. All tumors were negative for MUC4 and had an otherwise nonspecific immunophenotype. Of the 6 cases with available follow-up information, 2 had local recurrences, and 2 developed soft tissue and/or bone metastases, including 1 of them died of the disease.
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PMID:Recurrent YAP1 and KMT2A Gene Rearrangements in a Subset of MUC4-negative Sclerosing Epithelioid Fibrosarcoma. 3159 98

Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive neoplasm typically presenting with widespread involvement of the abdominopelvic peritoneum of adolescent males, usually without organ-based primary. Although it is believed to originate from the serous (mainly peritoneal) membranes, intracranial, sinonasal, intraosseous, and other soft tissue sites are also documented. A chromosomal translocation t(11:22)(p13;q12) signature that fuses EWSR1 and WT1 genes results in the production of a chimeric protein with transcriptional regulatory activity that drives oncogenesis. Integration of clinical, morphologic, immunohistochemical, and genetic data is necessary to arrive at the correct diagnosis, especially when the tumor arises in an atypical site. A 15-year-old male presented with hematuria and was found to have a large renal tumor associated with adrenal, liver, lung, and bone metastases. Histopathologic and immunophenotypic features were distinctive for DSRCT. This diagnosis was confirmed by means of fluorescence in situ hybridization and cytogenetic analysis, which documented the pathognomonic t(11;22) translocation, and by reverse transcription polymerase chain reaction on snap-frozen tissue, which revealed the EWSR1/WT1-specific chimeric transcript. Despite high-dose chemotherapy and radiation therapy targeted to a single T11 vertebral metastasis, the disease progressed, and the patient died 4 years after the diagnosis. A search of electronic databases for DSRCT yielded 16 cases of well-documented renal primaries out of around 1570 cases from all sites gathered from the global literature. Desmoplastic small round blue cell tumor and other primary renal tumors considered in the differential diagnosis with DSRCT are discussed.
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PMID:Desmoplastic Small Round Cell Tumor of the Kidney: Report of a Case, Literature Review, and Comprehensive Discussion of the Distinctive Morphologic, Immunohistochemical, and Molecular Features in the Differential Diagnosis of Small Round Cell Tumors Affecting the Kidney. 3280 6