Original Article

Oncogene (2008) 27, 2015–2026; doi:10.1038/sj.onc.1210836; published online 8 October 2007

MicroRNA expression signature of human sarcomas

S Subramanian1, W O Lui1, C H Lee1,2, I Espinosa1, T O Nielsen2, M C Heinrich3, C L Corless4, A Z Fire1,5 and M van de Rijn1

  1. 1Department of Pathology, Stanford University, Stanford, CA, USA
  2. 2Genetic Pathology Evaluation Centre, University of British Columbia, Vancouver, Canada
  3. 3Division of Hematology/Oncology, Oregon Health and Science University, Portland, OR, USA
  4. 4Department of Pathology, Oregon Health and Science University, Portland, OR, USA
  5. 5Department of Genetics, Stanford University, Stanford, CA, USA

Correspondence: Professor M van de Rijn, Department of Pathology, Stanford University Medical Center, 300 Pasteur Drive, L-235, Stanford, CA 94305, USA. E-mail: mrijn@stanford.edu

Received 10 May 2007; Revised 10 August 2007; Accepted 1 September 2007; Published online 8 October 2007.

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Abstract

MicroRNAs (miRNAs) are approx22 nucleotide-long noncoding RNAs involved in several biological processes including development, differentiation and proliferation. Recent studies suggest that knowledge of miRNA expression patterns in cancer may have substantial value for diagnostic and prognostic determinations as well as for eventual therapeutic intervention. We performed comprehensive analysis of miRNA expression profiles of 27 sarcomas, 5 normal smooth muscle and 2 normal skeletal muscle tissues using microarray technology and/or small RNA cloning approaches. The miRNA expression profiles are distinct among the tumor types as demonstrated by an unsupervised hierarchical clustering, and unique miRNA expression signatures were identified in each tumor class. Remarkably, the miRNA expression patterns suggested that two of the sarcomas had been misdiagnosed and this was confirmed by reevaluation of the tumors using histopathologic and molecular analyses. Using the cloning approach, we also identified 31 novel miRNAs or other small RNA effectors in the sarcomas and normal skeletal muscle tissues examined. Our data show that different histological types of sarcoma have distinct miRNA expression patterns, reflecting the apparent lineage and differentiation status of the tumors. The identification of unique miRNA signatures in each tumor type may indicate their role in tumorigenesis and may aid in diagnosis of soft tissue sarcomas.

Keywords:

miRNA, microarrays, sarcoma

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