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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.

Expression signatures of TP53 mutations in serous ovarian cancers