MicroRNA expression profiles classify human cancers (original) (raw)

• Letter
• Published: 09 June 2005
• Gad Getz1 na1,
• Eric A. Miska2 na1 nAff8,
• Ezequiel Alvarez-Saavedra2,
• Justin Lamb1,
• David Peck1,
• Alejandro Sweet-Cordero3,4,
• Benjamin L. Ebert1,4,
• Raymond H. Mak1,4,
• Adolfo A. Ferrando4,
• James R. Downing5,
• Tyler Jacks2,3,
• H. Robert Horvitz2,6 &
• …
• Todd R. Golub1,4,6

Nature volume 435, pages 834–838 (2005)Cite this article

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Abstract

Recent work has revealed the existence of a class of small non-coding RNA species, known as microRNAs (miRNAs), which have critical functions across various biological processes1,2. Here we use a new, bead-based flow cytometric miRNA expression profiling method to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers. The miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours. We observe a general downregulation of miRNAs in tumours compared with normal tissues. Furthermore, we were able to successfully classify poorly differentiated tumours using miRNA expression profiles, whereas messenger RNA profiles were highly inaccurate when applied to the same samples. These findings highlight the potential of miRNA profiling in cancer diagnosis.

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Acknowledgements

We thank E. Lander for critical review of the manuscript, S. Ramaswamy for discussions, and J.-P. Brunet, S. Monti, C. Ladd-Acosta and S. Shurtleff for computational help and technical assistance. We also thank J. Jacobson and Luminex Corporation for advice and technical support. E.A.M. was supported by the Howard Hughes Medical Institute. H.R.H., T.J. and T.R.G. are Investigators of the Howard Hughes Medical Institute.

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Author notes

1. Eric A. Miska
   Present address: Wellcome Trust/Cancer Research UK, Gurdon Institute, University of Cambridge, Cambridge, CB2 1QN, UK
2. Jun Lu, Gad Getz and Eric A. Miska: *These authors contributed equally to this work

Authors and Affiliations

1. Broad Institute of MIT and Harvard, Massachusetts, 02141, Cambridge, USA
   Jun Lu, Gad Getz, Justin Lamb, David Peck, Benjamin L. Ebert, Raymond H. Mak & Todd R. Golub
2. Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology,
   Eric A. Miska, Ezequiel Alvarez-Saavedra, Tyler Jacks & H. Robert Horvitz
3. MIT Center for Cancer Research, Massachusetts, 02139, Cambridge, USA
   Alejandro Sweet-Cordero & Tyler Jacks
4. Department of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Massachusetts, 02115, Boston, USA
   Jun Lu, Alejandro Sweet-Cordero, Benjamin L. Ebert, Raymond H. Mak, Adolfo A. Ferrando & Todd R. Golub
5. Department of Pathology, St. Jude Children's Research Hospital, Tennessee, 38105, Memphis, USA
   James R. Downing
6. Howard Hughes Medical Institute, Harvard Medical School, Massachusetts, 02115, Boston, USA
   H. Robert Horvitz & Todd R. Golub

Authors

1. Jun Lu
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2. Gad Getz
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3. Eric A. Miska
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4. Ezequiel Alvarez-Saavedra
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5. Justin Lamb
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6. David Peck
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7. Alejandro Sweet-Cordero
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8. Benjamin L. Ebert
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9. Raymond H. Mak
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10. Adolfo A. Ferrando
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11. James R. Downing
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12. Tyler Jacks
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13. H. Robert Horvitz
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14. Todd R. Golub
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Corresponding author

Correspondence toTodd R. Golub.

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Competing interests

miRNA expression data have been submitted to the Gene Expression Omnibus under the series accession number GSE2564. Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

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Lu, J., Getz, G., Miska, E. et al. MicroRNA expression profiles classify human cancers.Nature 435, 834–838 (2005). https://doi.org/10.1038/nature03702

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• Received: 02 February 2005
• Accepted: 05 May 2005
• Issue Date: 09 June 2005
• DOI: https://doi.org/10.1038/nature03702

Editorial Summary

MicroRNA in cancer

MicroRNAs are regulatory, non-coding RNAs about 22 nucleotides in length: over 200 have been identified in humans, and their functions are beginning to be pinned down. It has been suggested that like other regulatory molecules they might be involved in tumour formation, and three papers in this issue confirm that this is the case. One cluster of microRNAs, known as mir-17–92, is shown to be a potential oncogene by its action in an in vivo model of human B-cell lymphoma. A cluster of microRNAs on human chromosome 13 has been found to be regulated by c-Myc, an important transcription factor that is overexpressed in many human cancers. And analysis of microRNA expression in over 300 individuals shows that microRNA profiles could be of value in cancer diagnosis. There is a global downregulation of microRNA in tumours, and the microRNA profile also reflects the origin and differentiation state of the tumours.

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