Grant Number:	1R01CA172404-01A1 Interpret this number
Primary Investigator:	Ramus, Susan
Organization:	University Of Southern California
Project Title:	Identifying Prognostic Markers and Therapeutic Targets for Serous Ovarian Cancer
Fiscal Year:	2013

DESCRIPTION (provided by applicant): High-grade serous ovarian cancer (HGSOC) is the most common type of ovarian cancer and has very poor survival, as the tumors quickly become resistant to the current drug treatments. The Cancer Genome Atlas (TCGA) project has performed tumor profiling of ~500 HGSOC cases. From the expression analysis TCGA has recently identified a panel of genes that can be used to predict survival. Although the panel of genes validate in other studies many of the individual genes do not show consistent results across studies. To identify validated prognostic markers suitable to use as drug targets will require discovery in a larger set of tumors followed by validation in a very large series of samples. We have established the Ovarian Tumor Tissue Analysis (OTTA) consortium, an international collaboration of 30 studies with approximately 8,000 ovarian tumors and extensive clinical data. The majority of these tumors is from cases participating in the Ovarian Cancer Association Consortium (OCAC) and therefore have genotyping data on 200,000 single nucleotide polymorphisms (SNPs) and epidemiological data. We have identified SNPs that are associated with survival from our genome wide association study (GWAS) and preliminary data suggests that these germline changes may help to identify novel genes that may also be important somatic prognostic factors. We will utilize these existing datasets from TCGA, OTTA and OCAC to identify candidate prognostic genes and validate these genes in samples from OTTA. These biomarkers could be useful in the clinical setting for type of treatment and decision-making in recurrence and they will also provide a much-needed understanding of the biology of the disease. The specific aims of the proposal are: Aim 1: To identify candidate prognostic genes from a meta-analysis of expression data including subgroups of HGSOC and from an analysis of our survival GWAS. Aim 2: To perform expression analysis of 400 genes using the Nanostring platform on thousands of primary tumors to identify prognostic markers and to subtype the tumors. Aim 3: To reanalyze the survival GWAS data using the subgroups of the tumors and identify novel changes associated with survival. Aim 4: To test the identified genes and pathways in novel ovarian cancer models to determine if they could be used as targets for new drug treatments.




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PMID: 38837893
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Concurrent RB1 loss and BRCA-deficiency predicts enhanced immunological response and long-term survival in tubo-ovarian high-grade serous carcinoma.
Authors: Saner F.A.M. , Takahashi K. , Budden T. , Pandey A. , Ariyaratne D. , Zwimpfer T.A. , Meagher N.S. , Fereday S. , Twomey L. , Pishas K.I. , et al. .
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EPub date: 2023-11-10 00:00:00.0.
PMID: 37986741
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Methylation Signature Implicated in Immuno-Suppressive Activities in Tubo-Ovarian High-Grade Serous Carcinoma.
Authors: Wang C. , Block M.S. , Cunningham J.M. , Sherman M.E. , McCauley B.M. , Armasu S.M. , Vierkant R.A. , Traficante N. , Australian Ovarian Cancer Study Group , Talhouk A. , et al. .
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Increased FOXJ1 protein expression is associated with improved overall survival in high-grade serous ovarian carcinoma: an Ovarian Tumor Tissue Analysis Consortium Study.
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CCNE1 and survival of patients with tubo-ovarian high-grade serous carcinoma: An Ovarian Tumor Tissue Analysis consortium study.
Authors: Kang E.Y. , Weir A. , Meagher N.S. , Farrington K. , Nelson G.S. , Ghatage P. , Lee C.H. , Riggan M.J. , Bolithon A. , Popovic G. , et al. .
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Into the future: A pilot study combining imaging with molecular profiling to predict resectability in ovarian cancer.
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MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma.
Authors: Kang E.Y. , Millstein J. , Popovic G. , Meagher N.S. , Bolithon A. , Talhouk A. , Chiu D.S. , Anglesio M.S. , Leung B. , Tang K. , et al. .
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Development and validation of the gene-expression Predictor of high-grade-serous Ovarian carcinoma molecular subTYPE (PrOTYPE).
Authors: Talhouk A. , George J. , Wang C. , Budden T. , Tan T.Z. , Chiu D.S. , Kommoss S. , Leong H.S. , Chen S. , Intermaggio M.P. , et al. .
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Prognostic gene expression signature for high-grade serous ovarian cancer.
Authors: Millstein J. , Budden T. , Goode E.L. , Anglesio M.S. , Talhouk A. , Intermaggio M.P. , Leong H.S. , Chen S. , Elatre W. , Gilks B. , et al. .
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Molecular classification of epithelial ovarian cancer based on methylation profiling: evidence for survival heterogeneity.
Authors: Bodelon C. , Killian J.K. , Sampson J.N. , Anderson W.F. , Matsuno R. , Brinton L.A. , Lissowska J. , Anglesio M.S. , Bowtell D.D.L. , Doherty J.A. , et al. .
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Association of p16 expression with prognosis varies across ovarian carcinoma histotypes: an Ovarian Tumor Tissue Analysis consortium study.
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BRAF Mutations Occur Infrequently in Ovarian Cancer but Suggest Responsiveness to BRAF and MEK Inhibition.
Authors: Campos M.P. , Cohen M. , Von Euw E. , Velculescu V. , Kujak J.L. , Conklin D. , Hallberg D. , Slamon D.J. , Elvin J. , Konecny G.E. .
Source: Jco Precision Oncology, 2018; 2, .
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Single-Patient Molecular Testing with NanoString nCounter Data Using a Reference-Based Strategy for Batch Effect Correction.
Authors: Talhouk A. , Kommoss S. , Mackenzie R. , Cheung M. , Leung S. , Chiu D.S. , Kalloger S.E. , Huntsman D.G. , Chen S. , Intermaggio M. , et al. .
Source: Plos One, 2016; 11(4), p. e0153844.
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Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk.
Authors: Kar S.P. , Tyrer J.P. , Li Q. , Lawrenson K. , Aben K.K. , Anton-Culver H. , Antonenkova N. , Chenevix-Trench G. , Australian Cancer Study , Australian Ovarian Cancer Study Group , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2015 Oct; 24(10), p. 1574-84.
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