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Title: Functional genomics identifies five distinct molecular subtypes with clinical relevance and pathways for growth control in epithelial ovarian cancer
Authors: 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. 
Mori, S. 
Keywords: Cell line model for subtype
Functional genomic screen
Molecular subtype
Ovarian cancer
Issue Date: Jul-2013
Citation: 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., Mori, S. (2013-07). Functional genomics identifies five distinct molecular subtypes with clinical relevance and pathways for growth control in epithelial ovarian cancer. EMBO Molecular Medicine 5 (7) : 983-998. ScholarBank@NUS Repository.
Abstract: 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. Ovarian carcinomas remain a leading cause of cancer death among woman worldwide. Here, a novel rational patient stratification is proposed to unravel the heterogeneity of these cancers and provide means to guide novel intervention strategies. © 2013 The Authors.
Source Title: EMBO Molecular Medicine
ISSN: 17574676
DOI: 10.1002/emmm.201201823
Appears in Collections:Staff Publications

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