Enhanced GAB2 Expression Is Associated with Improved Survival in High-Grade Serous Ovarian Cancer and Sensitivity to PI3K Inhibition
- Author(s)
- Davis, SJ; Sheppard, KE; Anglesio, MS; George, J; Traficante, N; Fereday, S; Intermaggio, MP; Menon, U; Gentry-Maharaj, A; Lubinski, J; Gronwald, J; Pearce, CL; Pike, MC; Wu, A; Kommoss, S; Pfisterer, J; du Bois, A; Hilpert, F; Ramus, SJ; Bowtell, DDL; Huntsman, DG; Pearson, RB; Simpson, KJ; Campbell, IG; Gorringe, KL;
- Details
- Publication Year 2015-06,Volume 14,Issue #6,Page 1495-503
- Journal Title
- Molecular Cancer Therapeutics
- Publication Type
- Research article
- Abstract
- Identification of genomic alterations defining ovarian carcinoma subtypes may aid the stratification of patients to receive targeted therapies. We characterized high-grade serous ovarian carcinoma (HGSC) for the association of amplified and overexpressed genes with clinical outcome using gene expression data from 499 HGSC patients in the Ovarian Tumor Tissue Analysis cohort for 11 copy number amplified genes: ATP13A4, BMP8B, CACNA1C, CCNE1, DYRK1B, GAB2, PAK4, RAD21, TPX2, ZFP36, and URI. The Australian Ovarian Cancer Study and The Cancer Genome Atlas datasets were also used to assess the correlation between gene expression, patient survival, and tumor classification. In a multivariate analysis, high GAB2 expression was associated with improved overall and progression-free survival (P = 0.03 and 0.02), whereas high BMP8B and ATP13A4 were associated with improved progression-free survival (P = 0.004 and P = 0.02). GAB2 overexpression and copy number gain were enriched in the AOCS C4 subgroup. High GAB2 expression correlated with enhanced sensitivity in vitro to the dual PI3K/mTOR inhibitor PF-04691502 and could be used as a genomic marker for identifying patients who will respond to treatments inhibiting PI3K signaling.
- Publisher
- American Association for Cancer Research
- Keywords
- Adaptor Proteins, Signal Transducing/*genetics/metabolism; Adult; Aged; Aged, 80 and over; Cell Line, Tumor; Cell Survival/drug effects/genetics; Cystadenocarcinoma, Serous/*genetics/metabolism/therapy; DNA Copy Number Variations; Disease-Free Survival; Female; Gene Amplification; Gene Expression Profiling; *Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Kaplan-Meier Estimate; Middle Aged; Multivariate Analysis; Neoplasm Grading; Ovarian Neoplasms/*genetics/metabolism/therapy; *Phosphoinositide-3 Kinase Inhibitors; Pyridones/*pharmacology; Pyrimidines/*pharmacology; Young Adult
- Department(s)
- Laboratory Research
- Publisher's Version
- https://doi.org/10.1158/1535-7163.MCT-15-0039
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
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Last Modified: 2025-06-10 05:37:12