%0 Journal Article
%T Expression signatures of TP53 mutations in serous ovarian cancers
%A Marcus Q Bernardini
%A Tsukasa Baba
%A Paula S Lee
%A Jason C Barnett
%A Gregory P Sfakianos
%A Angeles Secord
%A Susan K Murphy
%A Edwin Iversen
%A Jeffrey R Marks
%A Andrew Berchuck
%J BMC Cancer
%D 2010
%I BioMed Central
%R 10.1186/1471-2407-10-237
%X 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.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.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.The TP53 tumor suppressor gene encodes a transcription factor that plays a critical role in regulating cell cycle progression, DNA repair, and cell death. TP53 is the most frequently altered gene in human cancers and loss of functional p53 protein occurs in a majority of epithelial ovarian cancers. Ovarian cancers with serous histology account for about two-thirds of the incident disease and these cases usually present at an advanced stage leading to a very high mortality rate. In studies in which full gene sequencing has been performed, 60-70% of both early and advanced stage serous ovarian cancers harbor TP53 mutations [1,2]. In contrast, other histological subtypes of epithelial ovarian cancer that more commonly present at an early stage (endometrioid, clear cell, mucinous) hav
%U http://www.biomedcentral.com/1471-2407/10/237