Rapid, reliable, and reproducible molecular sub-grouping of clinical medulloblastoma samples
Top Cited Papers
Open Access
- 6 November 2011
- journal article
- research article
- Published by Springer Nature in Acta Neuropathologica
- Vol. 123 (4) , 615-626
- https://doi.org/10.1007/s00401-011-0899-7
Abstract
The diagnosis of medulloblastoma likely encompasses several distinct entities, with recent evidence for the existence of at least four unique molecular subgroups that exhibit distinct genetic, transcriptional, demographic, and clinical features. Assignment of molecular subgroup through routine profiling of high-quality RNA on expression microarrays is likely impractical in the clinical setting. The planning and execution of medulloblastoma clinical trials that stratify by subgroup, or which are targeted to a specific subgroup requires technologies that can be economically, rapidly, reliably, and reproducibly applied to formalin-fixed paraffin embedded (FFPE) specimens. In the current study, we have developed an assay that accurately measures the expression level of 22 medulloblastoma subgroup-specific signature genes (CodeSet) using nanoString nCounter Technology. Comparison of the nanoString assay with Affymetrix expression array data on a training series of 101 medulloblastomas of known subgroup demonstrated a high concordance (Pearson correlation r = 0.86). The assay was validated on a second set of 130 non-overlapping medulloblastomas of known subgroup, correctly assigning 98% (127/130) of tumors to the appropriate subgroup. Reproducibility was demonstrated by repeating the assay in three independent laboratories in Canada, the United States, and Switzerland. Finally, the nanoString assay could confidently predict subgroup in 88% of recent FFPE cases, of which 100% had accurate subgroup assignment. We present an assay based on nanoString technology that is capable of rapidly, reliably, and reproducibly assigning clinical FFPE medulloblastoma samples to their molecular subgroup, and which is highly suited for future medulloblastoma clinical trials.Keywords
This publication has 18 references indexed in Scilit:
- Pediatric and adult sonic hedgehog medulloblastomas are clinically and molecularly distinctActa Neuropathologica, 2011
- mRNA transcript quantification in archival samples using multiplexed, color-coded probesBMC Biotechnology, 2011
- Integrative Genomic Analysis of Medulloblastoma Identifies a Molecular Subgroup That Drives Poor Clinical OutcomeJournal of Clinical Oncology, 2011
- Digital Multiplexed Gene Expression Analysis Using the NanoString nCounter SystemCurrent Protocols in Molecular Biology, 2011
- Rapid Diagnosis of Medulloblastoma Molecular SubgroupsClinical Cancer Research, 2011
- Medulloblastoma: clinicopathological correlates of SHH, WNT, and non-SHH/WNT molecular subgroupsActa Neuropathologica, 2011
- Multiplexed measurements of gene signatures in different analytes using the Nanostring nCounter™ Assay SystemBMC Research Notes, 2009
- Integrated Genomics Identifies Five Medulloblastoma Subtypes with Distinct Genetic Profiles, Pathway Signatures and Clinicopathological FeaturesPLOS ONE, 2008
- Direct multiplexed measurement of gene expression with color-coded probe pairsNature Biotechnology, 2008
- Diagnosis of multiple cancer types by shrunken centroids of gene expressionProceedings of the National Academy of Sciences, 2002