Functional genomics identifies five distinct molecular subtypes with clinical relevance and pathways for growth control in epithelial ovarian cancer
Open Access
- 13 May 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in EMBO Molecular Medicine
- Vol. 5 (7), 1051-1066
- https://doi.org/10.1002/emmm.201201823
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.This publication has 79 references indexed in Scilit:
- Integrated genomic analyses of ovarian carcinomaNature, 2011
- Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1Cancer Cell, 2010
- A Gene Signature Predictive for Outcome in Advanced Ovarian Cancer Identifies a Survival Factor: Microfibril-Associated Glycoprotein 2Cancer Cell, 2009
- Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1Nature, 2009
- PAX2 expression in low malignant potential ovarian tumors and low-grade ovarian serous carcinomasLaboratory Investigation, 2009
- The biology of ovarian cancer: new opportunities for translationNature Reviews Cancer, 2009
- A collection of breast cancer cell lines for the study of functionally distinct cancer subtypesCancer Cell, 2006
- GenePattern 2.0Nature Genetics, 2006
- Oncogenic pathway signatures in human cancers as a guide to targeted therapiesNature, 2005
- Distinct types of diffuse large B-cell lymphoma identified by gene expression profilingNature, 2000