MicroRNA-based Assay for Diagnosing Tumor Tissue Origin
S Rosenwald, I Barshak, D Lebanony, H Gibory, L Cohen, Y Goren, I Leizerman, D Nonaka, A Tobar, Z Bentwich, R Aharonov, N Rosenfeld, D Cohen. Rosetta Genomics, Rehovot, Israel; Sheba Medical Center, Tel-Hashomer, Israel; Tel-Aviv University, Tel-Aviv, Israel
Background: Cancer of unknown primary (CUP) constitutes 3%5% of all newly diagnosed cancer cases. It presents a major diagnostic challenge due to the therapeutic implications of the tissue origin of the cancer. MicroRNAs are a family of non-coding, regulatory RNA genes that are involved in oncogenesis and show remarkable tissue-specificity. In previous work we demonstrated that using a set of only 48 microRNAs with a biologically-motivated classification procedure, tissue of origin could be identified with high accuracy. Here we develop this potential of microRNA into a practical diagnostic assay.
Design: Hundreds of primary and metastatic tumor FFPE samples were collected. High-quality RNA, including the well-preserved microRNA fraction, was extracted from the FFPE blocks using proprietary protocols. Expression levels of potential microRNA biomarkers were profiled using a sensitive and specific qRT-PCR platform. Advanced classification algorithms were developed to utilize the information of the microRNA expression patterns for the diagnosis of tumor origin.
Results: Using expression levels of a panel of microRNAs in qRT-PCR, tissue of origin could be accurately identified and a diagnostic assay based on this technology was defined. The performance of the assay was validated using an independent test set.
Conclusions: Previous studies have highlighted the tissue-specificity of microRNA expression, and have demonstrated the potential of microRNA expression for accurate identification of tumor tissue of origin. Here we developed this potential into a diagnostic assay, based on a qRT-PCR platform. This assay produces reproducible, accurate results, and provides an important new tool for diagnosing tumor tissue origin.
Category: Special Category for 2009 - Pan-genomic/Pan-proteomic approaches to Cancer
Monday, March 9, 2009 2:45 PM
Platform Session: Section G, Monday Afternoon