These authors contributing equally to this work.
Functional genomics identifies five distinct molecular subtypes with clinical relevance and pathways for growth control in epithelial ovarian cancer
Article first published online: 13 MAY 2013
Copyright © 2013 EMBO Molecular Medicine
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
EMBO Molecular Medicine
Volume 5, Issue 7, pages 1051–1066, July 2013
How to Cite
Tan, T. Z., Miow, Q. H., Huang, R. Y.-J., Wong, M. K., Ye, J., Lau, J. A., Wu, M. C., Bin Abdul Hadi, L. H., Soong, R., Choolani, M., Davidson, B., Nesland, J. M., Wang, L.-Z., Matsumura, N., Mandai, M., Konishi, I., Goh, B.-C., Chang, J. T., Thiery, J. P. and Mori, S. (2013), Functional genomics identifies five distinct molecular subtypes with clinical relevance and pathways for growth control in epithelial ovarian cancer. EMBO Mol Med, 5: 1051–1066. doi: 10.1002/emmm.201201823
- Issue published online: 3 JUL 2013
- Article first published online: 13 MAY 2013
- Manuscript Accepted: 9 APR 2013
- Manuscript Revised: 3 APR 2013
- Manuscript Received: 6 AUG 2012
- Cancer Science Institute of Singapore, Institute of Molecular Cellular Biology at A*STAR
- Vehicle Racing Commemorative Foundation in Japan
- Princess Takamatsu Cancer Research Fund
- cell line model for subtype;
- functional genomic screen;
- molecular subtype;
- ovarian cancer;
Epithelial ovarian cancer (EOC) is hallmarked by a high degree of heterogeneity. To address this heterogeneity, a classification scheme was developed based on gene expression patterns of 1538 tumours. Five, biologically distinct subgroups — Epi-A, Epi-B, Mes, Stem-A and Stem-B — exhibited significantly distinct clinicopathological characteristics, deregulated pathways and patient prognoses, and were validated using independent datasets. To identify subtype-specific molecular targets, ovarian cancer cell lines representing these molecular subtypes were screened against a genome-wide shRNA library. Focusing on the poor-prognosis Stem-A subtype, we found that two genes involved in tubulin processing, TUBGCP4 and NAT10, were essential for cell growth, an observation supported by a pathway analysis that also predicted involvement of microtubule-related processes. Furthermore, we observed that Stem-A cell lines were indeed more sensitive to inhibitors of tubulin polymerization, vincristine and vinorelbine, than the other subtypes. This subtyping offers new insights into the development of novel diagnostic and personalized treatment for EOC patients.