Efficient molecular subtype classification of high‐grade serous ovarian cancer
Abstract
High‐grade serous carcinomas (HGSCs) account for approximately 70% of all epithelial ovarian cancers diagnosed. Using microarray gene expression profiling, we previously identified four molecular subtypes of HGSC: C1 (mesenchymal), C2 (immunoreactive), C4 (differentiated), and C5 (proliferative), which correlate with patient survival and have distinct biological features. Here, we describe molecular classification of HGSC based on a limited number of genes to allow cost‐effective and high‐throughput subtype analysis. We determined a minimal signature for accurate classification, including 39 differentially expressed and nine control genes from microarray experiments. Taqman‐based (low‐density arrays and Fluidigm), fluorescent oligonucleotides (Nanostring), and targeted RNA sequencing (Illumina) assays were then compared for their ability to correctly classify fresh and formalin‐fixed, paraffin‐embedded samples. All platforms achieved > 90% classification accuracy with RNA from fresh frozen samples. The Illumina and Nanostring assays were superior with fixed material. We found that the C1, C2, and C4 molecular subtypes were largely consistent across multiple surgical deposits from individual chemo‐naive patients. In contrast, we observed substantial subtype heterogeneity in patients whose primary ovarian sample was classified as C5. The development of an efficient molecular classifier of HGSC should enable further biological characterization of molecular subtypes and the development of targeted clinical trials. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 30, 2015
- Source ID
- 10.1002/path.4536
Entities
People
- Dariush Etemadmoghadam
- David Bowtell
- Huei San Leong
- Joshy George
- Laura Galletta
- Martin Köbel
- Susan J. Ramus
- The Australian Ovarian Cancer Study
Organizations
- Cancer Council Australia
- Cancer Council New South Wales
- Cancer Council SA
- Cancer Council Tasmania
- Cancer Council Victoria
- Imperial College London
- Jackson Laboratory
- National Health and Medical Research Council
- Ovarian Cancer Australia
- Peter MacCallum Cancer Centre
- United States Army Medical Research and Development Command
- United States Department of Defense
- University of Calgary
- University of Melbourne