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MicroRNAs accurately identify cancer tissue origin

Rosenfeld, Nitzan, Aharonov, Ranit, Meiri, Eti, Rosenwald, Shai, Spector, Yael, Zepeniuk, Merav, Benjamin, Hila, Shabes, Norberto, Tabak, Sarit, Levy, Asaf, Lebanony, Danit, Goren, Yaron, Silberschein, Erez, Targan, Nurit, Ben-Ari, Alex, Gilad, Shlomit, Sion-Vardy, Netta, Tobar, Ana, Feinmesser, Meora, Kharenko, Oleg, Nativ, Ofer, Nass, Dvora, Perelman, Marina, Yosepovich, Ady, Shalmon, Bruria, Polak-Charcon, Sylvie, Fridman, Eddie, Avniel, Amir, Bentwich, Isaac, Bentwich, Zvi, Cohen, Dalia, Chajut, Ayelet, Barshack, Iris·2008·Nature Biotechnology
DOI 10.1038/nbt1392
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Abstract

MicroRNAs (miRNAs) belong to a class of noncoding, regulatory RNAs that is involved in oncogenesis and shows remarkable tissue specificity. Their potential for tumor classification suggests they may be used in identifying the tissue in which cancers of unknown primary origin arose, a major clinical problem. We measured miRNA expression levels in 400 paraffin-embedded and fresh-frozen samples from 22 different tumor tissues and metastases. We used miRNA microarray data of 253 samples to construct a transparent classifier based on 48 miRNAs. Two-thirds of samples were classified with high confidence, with accuracy >90%. In an independent blinded test-set of 83 samples, overall high-confidence accuracy reached 89%. Classification accuracy reached 100% for most tissue classes, including 131 metastatic samples. We further validated the utility of the miRNA biomarkers by quantitative RT-PCR using 65 additional blinded test samples. Our findings demonstrate the effectiveness of miRNAs as biomarkers for tracing the tissue of origin of cancers of unknown primary origin.

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Metadata

Authors
Rosenfeld, N., Aharonov, R., Meiri, E., Rosenwald, S., Spector, Y., Zepeniuk, M., Benjamin, H., Shabes, N., Tabak, S., Levy, A., Lebanony, D., Goren, Y., Silberschein, E., Targan, N., Ben-Ari, A., Gilad, S., Sion-Vardy, N., Tobar, A., Feinmesser, M., Kharenko, O., Nativ, O., Nass, D., Perelman, M., Yosepovich, A., Shalmon, B., Polak-Charcon, S., Fridman, E., Avniel, A., Bentwich, I., Bentwich, Z., Cohen, D., Chajut, A., & Barshack, I.
Venue
Nature Biotechnology
Publisher
Springer Science and Business Media LLC
Published
2008-03-23
Volume
26
Issue
4
Pages
462-469
ISSN
  • 1087-0156
  • 1546-1696
DOI
10.1038/nbt1392
Cited by
812
References
3
Language
en
Licence
www.springer.com/tdm (tdm)

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