Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0035412 (rhabdomyosarcoma)
 6,156 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amplification of cellular oncogenes may be important for the development and progression of malignant tumors. In human sarcomas, amplification of several genes located to the q13-14 region of chromosome 12 has been reported. Because the mdm2 protein seems to inactivate the tumor suppressor protein p53, a selective growth advantage of 12q13-14 amplification has previously been assigned to increased copy number and expression of the MDM2 gene. We have analyzed a panel of 98 human sarcomas of different subtypes to characterize the 12q13-14 amplica and determine which of the genes GLI, A2MR, SAS, MDM2, and GADD153 (CHOP) in this region was most consistently amplified. MDM2 was amplified in 9 of the tumors, SAS in 10, GADD153 in 4, GLI in 2, and A2MR in 2. Amplification was, in most cases, associated with increased expression of the corresponding gene. SAS and MDM2 were coamplified in 8 of the tumors, whereas GADD153, GLI, and A2MR were only amplified together with SAS. One liposarcoma showed amplification of MDM2 alone, whereas two osteosarcomas and a rhabdomyosarcoma cell line showed amplification of SAS and GADD153 (CHOP) but not MDM2. It is suggested that the selective target for these amplica may be an as yet unidentified gene localized between SAS and MDM2.
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PMID:Mapping of amplification units in the q13-14 region of chromosome 12 in human sarcomas: some amplica do not include MDM2. 811 20

Rhabdomyosarcoma, the most common pediatric soft tissue malignancy arises in 2 major histologic forms: embryonal and alveolar. Classically, the alveolar subtype is characterized by a chromosomal translocation t(2;13)(q35;q14) or t(1;13)(p36;q14) fusing the PAX3 or PAX7 gene, respectively, to the FOXO1 gene, although fusion-negative cases of alveolar rhabdomyosarcoma (ARMS) occur; these share considerably more with the genomic profiles and biological behavior of embryonal rhabdomyosarcoma than with fusion-positive ARMS. The current understanding of any additional genetic aberrations in fusion-positive ARMS is limited. In this study, we evaluated tumor-specific copy number alterations in a cohort of fusion-positive ARMSs using high-resolution technology. The results presented here include previously described changes as well as completely novel findings of copy number alterations in BCR and DICER. The study furthermore highlights associations between fusion type and genotype, as well as outcomes and genotype. Rearrangement of PAX7 is strongly associated with copy number alteration of Glypican 5 (GPC5) and moderately with amplification of IGF1R. There is a moderate association between death from/relapse of disease and, on the one hand, amplification of 12q13.3 (DDIT3; Gli1), and on the other hand, copy number alteration of Wnt6 or LRP1B. Gains of both LRP1B and Gli1 in turn are strongly associated with MycN amplification.
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PMID:A study of alveolar rhabdomyosarcoma copy number alterations by single nucleotide polymorphism analysis. 2461 50

Break-apart FISH probes are the most popular and reliable type of FISH probes used to confirm certain pathological diagnoses. The interpretation is usually easy, however, in some instances it is not so unequivocal. Our aim was to reveal and elucidate the problems occurring in the process of evaluation of the break-apart probe results. Altogether 301 soft tissue sarcomas with confirmed molecular tests using break-apart probes were assessed to reveal the frequency and type of unusual signal pattern. Among 89 synovial sarcoma (SS18) 11%, 12 alveolar rhabdomyosarcoma (FOXO1) 50%, 53 myxoid liposarcoma (DDIT3) 7.5%, 6 low grade fibromyxoid sarcoma (FUS) 67%, 93 Ewing sarcoma (EWSR1) 3%, 12 clear cell sarcoma (EWSR1) 8%, 5 desmoplastic small round cell tumor (EWSR1) 0%, 9 extraskeletal myxoid chondrosarcoma (EWSR1) 0%, 2 myoepithelial carcinoma (EWSR1) 50%, 14 dermatofibrosarcoma protuberans (COL1A1) 86% and 6 nodular fasciitis (USP6) 17% atypical break-apart signals were detected. Despite the unusual signal pattern type, the fusion genes were detected using either metaphase FISH, interphase FISH with translocation/TriCheck probe or RT-PCR methods. Although the interpretation problems in the process to evaluate the break-apart probe results is well known from sporadic case reports, a systemic overview to detect their frequency has not been performed so far. In our work we highlighted the relative frequency of this problem and pinpointed those signal-patterns which, despite their unusual appearance, can still confirm the diagnosis.
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PMID:Unusual Signal Patterns of Break-apart FISH Probes Used in the Diagnosis of Soft Tissue Sarcomas. 2810 80

Conventional well-differentiated, dedifferentiated, and myxoid liposarcomas have long been known to harbor numerous typical genetic alterations that allow for diagnosis of these tumors. These include MDM2 and CDK4 amplification in well-differentiated and dedifferentiated liposarcomas as well as FUS-DDIT3 rearrangements in myxoid liposarcoma. More recently, in-frame TRIO-TERT fusion genes have been described in a subset of non-translocation-related sarcomas including myxofibrosarcoma, dedifferentiated liposarcoma, undifferentiated pleomorphic sarcoma, pleomorphic rhabdomyosarcoma, and leiomyosarcoma. These genetic rearrangements lead to TERT mRNA expression levels hundreds of times higher than normal, causing increased telomerase activation in these tumors. Herein, we describe an unusual case of a liposarcoma with spindle cell features and a TRIO-TERT fusion transcript identified through next-generation sequencing.
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PMID:Spindle cell liposarcoma with a TRIO-TERT fusion transcript. 3079 29