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Open Access Research article

Expression signatures of TP53 mutations in serous ovarian cancers

Marcus Q Bernardini1, Tsukasa Baba2, Paula S Lee2, Jason C Barnett2, Gregory P Sfakianos2, Angeles Alvarez Secord2, Susan K Murphy2, Edwin Iversen3, Jeffrey R Marks4 and Andrew Berchuck2*

Author Affiliations

1 Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Toronto, 600 University Avenue, Toronto, Ontario M5G 2M9 Canada

2 Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, Durham, NC 27708, USA

3 Department of Statistical Science, Duke University, Durham, NC 27708, USA

4 Department of Surgery, Duke University Medical Center, Durham, NC 27708, USA

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BMC Cancer 2010, 10:237  doi:10.1186/1471-2407-10-237

Published: 26 May 2010

Abstract

Background

Mutations in the TP53 gene are extremely common and occur very early in the progression of serous ovarian cancers. Gene expression patterns that relate to mutational status may provide insight into the etiology and biology of the disease.

Methods

The TP53 coding region was sequenced in 89 frozen serous ovarian cancers, 40 early stage (I/II) and 49 advanced stage (III/IV). Affymetrix U133A expression data was used to define gene expression patterns by mutation, type of mutation, and cancer stage.

Results

Missense or chain terminating (null) mutations in TP53 were found in 59/89 (66%) ovarian cancers. Early stage cancers had a significantly higher rate of null mutations than late stage disease (38% vs. 8%, p < 0.03). In advanced stage cases, mutations were more prevalent in short term survivors than long term survivors (81% vs. 30%, p = 0.0004). Gene expression patterns had a robust ability to predict TP53 status within training data. By using early versus late stage disease for out of sample predictions, the signature derived from early stage cancers could accurately (86%) predict mutation status of late stage cancers.

Conclusions

This represents the first attempt to define a genomic signature of TP53 mutation in ovarian cancer. Patterns of gene expression characteristic of TP53 mutation could be discerned and included several genes that are known p53 targets or have been described in the context of expression signatures of TP53 mutation in breast cancer.