The miR-17-92 cluster and its target THBS1 are differentially expressed in angiosarcomas dependent on MYC amplification

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. (June 2012) The miR-17-92 cluster and its target THBS1 are differentially expressed in angiosarcomas dependent on MYC amplification. Genes Chromosomes Cancer, 51 (6). pp. 569-78. ISSN 1098-2264 (Electronic)1045-2257 (Linking)

URL: https://www.ncbi.nlm.nih.gov/pubmed/22383169
DOI: 10.1002/gcc.21943

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.

Item Type: Paper
Uncontrolled Keywords: Adult Aged Aged, 80 and over Comparative Genomic Hybridization DNA-Binding Proteins/biosynthesis/genetics Female *Gene Amplification Gene Expression Regulation, Neoplastic *Genes, myc Hemangiosarcoma/chemistry/*genetics/metabolism Humans In Situ Hybridization, Fluorescence Male MicroRNAs/biosynthesis/*genetics Middle Aged Proto-Oncogene Proteins c-myc/biosynthesis/genetics Sequence Analysis, RNA Thrombospondin 1/biosynthesis/*genetics Transcription Factors/biosynthesis/genetics Vascular Neoplasms/chemistry/*genetics/metabolism
Subjects: diseases & disorders > cancer > cancer types > angiosarcoma
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene amplification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > miRNA
CSHL Authors:
Communities: CSHL labs > Maki lab
Depositing User: Matt Covey
Date: June 2012
Date Deposited: 20 Oct 2016 16:49
Last Modified: 20 Oct 2016 16:49
PMCID: PMC3360479
Related URLs:
URI: http://repository.cshl.edu/id/eprint/33737

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