Noerholm et al. BMC Cancer 2012, 12:22 http://www.biomedcentral.com/1471-2407/12/22 R E S E A R C H A R T I C L E Open Access RNA expression patterns in serum microvesicles from patients with glioblastoma multiforme and controls Mikkel Noerholm1,2*, Leonora Balaj1, Tobias Limperg1,3, Afshin Salehi1,4, Lin Dan Zhu1, Fred H Hochberg1, Xandra O Breakefield1, Bob S Carter1,4 and Johan Skog1,2 Abstract Background: RNA from exosomes and other microvesicles contain transcripts of tumour origin. In this study we sought to identify biomarkers of glioblastoma multiforme in microvesicle RNA from serum of affected patients. Methods: Microvesicle RNA from serum from patients with de-novo primary glioblastoma multiforme (N = 9) and normal controls (N = 7) were analyzed by microarray analysis. Samples were collected according to protocols approved by the Institutional Review Board. Differential expressions were validated by qRT-PCR in a separate set of samples (N = 10 in both groups). Results: Expression profiles of microvesicle RNA correctly separated individuals in two groups by unsupervised clustering. The most significant differences pertained to down-regulated genes (121 genes > 2-fold down) in the glioblastoma multiforme patient microvesicle RNA, validated by qRT-PCR on several genes. Overall, yields of microvesicle RNA from patients was higher than from normal controls, but the additional RNA was primarily of size < 500 nt. Gene ontology of the down-regulated genes indicated these are coding for ribosomal proteins and genes related to ribosome production. Conclusions: Serum microvesicle RNA from patients with glioblastoma multiforme has significantly down- regulated levels of RNAs coding for ribosome production, compared to normal healthy controls, but a large overabundance of RNA of unknown origin with size < 500 nt. Keywords: Exosomes, Microvesicles, Microarray, Biomarkers, Serum, Glioma Background Cancer molecular diagnostics is becoming increasingly important with the accumulating knowledge of the molecular mechanisms underlying various types of can- cers and the implications for treatment option selection and prognosis. For patients with glioblastoma multi- forme (GBM), treatment planning currently takes into account radiographic imaging, which documents volume and location of disease [1], and in some cases muta- tional analysis [2], methylation status of genomic DNA with particular emphasis on the DNA repair gene for * Correspondence: mikkel@exosomedx.com 1Department of Neurology, Neurosurgery and Radiology, Massachusetts General Hospital and Program in Neuroscience, Harvard Medical School, Boston, MA 02114, USA Full list of author information is available at the end of the article methyl guanidine methyl transferase (MGMT [3]) and gene expression patterns of the tumour, which allows the broad categorization of tumours that are histologi- cally similar into molecular subtypes [4]. To date most molecular studies have utilized primary explant cultures or frozen, formalin fixed tumour tissue derived at the time of surgical resection. These methods have the dis- advantage that the part of the tumour specimen chosen for analysis may not represent the rest of the tumour, and the molecular profile of the recurrent tumour may be very different from the original biopsy. It would be very useful to have a way to monitor and evaluate the tumour gene expression pattern over time in a non- invasive assay, such as through a blood sample test. Over the past few years a growing list of studies has reported on the ability to use expression profiling tests © 2012 Noerholm et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.