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A gene expression profile of BRCAness that is associated with outcome in ovarian cancer

ABSTRACT: A gene expression profile of BRCAness was defined in publicly available expression data of 61 patients with epithelial ovarian cancer (34 patients with BRCA-1 or BRCA-2 mutations and 27 patients with sporadic disease). This dataset is publicly available at http://jnci.oxfordjournals.org/cgi/content/full/94/13/990/DC1 The BRCAness profile was correlated with outcome in 70 patients with epithelial ovarian cancer and known outcome data. Correlation with outcome

ORGANISM(S): Homo sapiens

SUBMITTER: panagiotis konstantinopoulos

PROVIDER: E-GEOD-19829 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Gene expression profile of BRCAness that correlates with responsiveness to chemotherapy and with outcome in patients with epithelial ovarian cancer.

Konstantinopoulos Panagiotis A PA Spentzos Dimitrios D Karlan Beth Y BY Taniguchi Toshiyasu T Fountzilas Elena E Francoeur Nancy N Levine Douglas A DA Cannistra Stephen A SA

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20100614 22

<h4>Purpose</h4>To define a gene expression profile of BRCAness that correlates with chemotherapy response and outcome in epithelial ovarian cancer (EOC).<h4>Methods</h4>A publicly available microarray data set including 61 patients with EOC with either sporadic disease or BRCA(1/2) germline mutations was used for development of the BRCAness profile. Correlation with platinum responsiveness was assessed in platinum-sensitive and platinum-resistant tumor biopsy specimens from six patients with BR ...[more]

PMID: 20547991

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Project description:PURPOSE: We investigated whether tumor tissue obtained at diagnosis expresses a specific gene profile that is predictive of findings at second-look surgery in patients with epithelial ovarian cancer (EOC). PATIENTS AND METHODS: Tumor tissue obtained at the time of diagnosis was profiled with oligonucleotide microarrays. Class prediction analysis was performed in a training set of 24 patients who had undergone a second-look procedure. The resultant predictive signature was then tested on an independent validation set comprised of 36 patients. RESULTS: A 93-gene signature referred to as the Chemotherapy Response Profile (CRP) was identified through its association with pathologic complete response. When applied to a separate validation set, the CRP distinguished between patients with unfavorable versus favorable overall survival (median 41 months v not yet reached, respectively, log-rank P = .007), with a median follow-up of 52 months. The signature maintained independent prognostic value in multivariate analysis, controlling for other known prognostic factors such as age, stage, grade, and debulking status. There was no genetic overlap between the CRP and our previously described Ovarian Cancer Prognostic Profile (OCPP), which demonstrated similar prognostic value. The combination of the CRP and OCPP yielded better prognostic discrimination then either profile alone. Genes present in the CRP include BAX, a proapoptotic protein previously associated with chemotherapy response in ovarian cancer. CONCLUSION: Identification of a gene expression profile based on pathologic response in EOC provides independent prognostic information and offers potential insights into the mechanism of drug resistance. Efforts to identify a more tailored profile using selected genes from both the CRP and OCPP are underway. keyword(s): Correlation with outcome All microarray experiments were performed at the BIDMC Genomics Center. Ovarian cancer samples were collected at the time of primary debulking surgery and frozen at 80°C. Tumor samples were pulverized in liquid nitrogen and homogenized in Trizol solution, followed by RNA isolation, probe labeling, and Affymetrix GeneChip hybridization using standard manufacturer protocols. The dChip algorithm was used for data normalization and for generating gene expression signal values. Two outlier arrays as identified by the dChip software were excluded from further analysis.

Dataset Information

A gene expression profile of BRCAness that is associated with outcome in ovarian cancer

Publications

Gene expression profile of BRCAness that correlates with responsiveness to chemotherapy and with outcome in patients with epithelial ovarian cancer.

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