Functional genomics identifies five distinct molecular subtypes with clinical relevance and pathways for growth control in epithelial ovarian cancer. Issue 7 (13th May 2013)

• Record Type: Journal Article
• Authors: Tan, Tuan Zea; Miow, Qing Hao; Huang, Ruby Yun‐Ju; Wong, Meng Kang; Ye, Jieru; Lau, Jieying Amelia; Wu, Meng Chu; Bin Abdul Hadi, Luqman Hakim; Soong, Richie; Choolani, Mahesh; Davidson, Ben; Nesland, Jahn M.; Wang, Ling‐Zhi; Matsumura, Noriomi; Mandai, Masaki; Konishi, Ikuo; Goh, Boon‐Cher; Chang, Jeffrey T.; Thiery, Jean Paul; Mori, Seiichi
• Is Part Of: EMBO molecular medicine. Volume 5:Issue 7(2013:Jul.)
• Page Start: 1051
• Page End: 1066
• Publication Date: 2013-05-13
• Subjects: cell line model for subtype -- functional genomic screen -- molecular subtype -- ovarian cancer -- tubulin; Molecular biology -- Periodicals; Medical genetics -- Periodicals; Pathology, Molecular -- Periodicals; 616.04205
• DOI: 10.1002/emmm.201201823
• Languages: English
• ISSNs: 1757-4676

Abstract

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. Abstract : 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.