The miR-17-92 cluster and its target THBS1 are differentially expressed in angiosarcomas dependent on MYC amplification Journal Article
| Authors: | Italiano, A.; Thomas, R.; Breen, M.; Zhang, L.; Crago, A. M.; Singer, S.; Khanin, R.; Maki, R. G.; Mihailovic, A.; Hafner, M.; Tuschl, T.; Antonescu, C. R. |
| Article Title: | The miR-17-92 cluster and its target THBS1 are differentially expressed in angiosarcomas dependent on MYC amplification |
| Abstract: | Angiosarcomas (ASs) represent a heterogeneous group of malignant vascular tumors that may occur spontaneously as primary tumors or secondarily after radiation therapy or in the context of chronic lymphedema. Most secondary ASs have been associated with MYC oncogene amplification, whereas the role of MYC abnormalities in primary AS is not well defined. Twenty-two primary and secondary ASs were analyzed by array-comparative genomic hybridization (aCGH) and by deep sequencing of small RNA libraries. By aCGH and subsequently confirmed by fluorescence in situ hybridization, MYC amplification was identified in three out of six primary tumors and in 8 out of 12 secondary AS. We have also found MAML1 as a new potential oncogene in MYC-amplified AS. Significant upregulation of the miR-17-92 cluster was observed in MYC-amplified AS compared to AS lacking MYC amplification and the control group (other vascular tumors, nonvascular sarcomas). Moreover, MYC-amplified ASs were associated with a significantly lower expression of thrombospondin-1 (THBS1) than AS without MYC amplification or controls. Altogether, our study implicates MYC amplification not only in the pathogenesis of secondary AS but also in a subset of primary AS. Thus, MYC amplification may play a crucial role in the angiogenic phenotype of AS through upregulation of the miR-17-92 cluster, which subsequently downregulates THBS1, a potent endogenous inhibitor of angiogenesis. © 2012 Wiley Periodicals, Inc. |
| Keywords: | adult; clinical article; controlled study; aged; aged, 80 and over; middle aged; unclassified drug; gene sequence; dna-binding proteins; vascular neoplasms; phenotype; in situ hybridization, fluorescence; disease association; metastasis; reverse transcription polymerase chain reaction; microrna; gene amplification; gene expression; angiosarcoma; hemangiosarcoma; carcinogenesis; transcription factors; sarcoma; oncogene; gene expression regulation, neoplastic; fluorescence in situ hybridization; microarray analysis; myc protein; genes, myc; western blotting; vascular tumor; down regulation; real time polymerase chain reaction; upregulation; micrornas; sequence analysis, rna; thrombospondin 1; proto-oncogene proteins c-myc; comparative genomic hybridization; small nuclear rna; mir 17 92 |
| Journal Title: | Genes Chromosomes and Cancer |
| Volume: | 51 |
| Issue: | 6 |
| ISSN: | 1045-2257 |
| Publisher: | Wiley Periodicals, Inc |
| Date Published: | 2012-06-01 |
| Start Page: | 569 |
| End Page: | 578 |
| Language: | English |
| DOI: | 10.1002/gcc.21943 |
| PROVIDER: | scopus |
| PUBMED: | 22383169 |
| PMCID: | PMC3360479 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 May 2012" - "CODEN: GCCAE" - "Source: Scopus" |
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