Expression signatures of TP53 mutations in serous ovarian cancers.
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.
Bernardini
Marcus Q
MQ
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Toronto, 600 University Avenue, Toronto, Ontario M5G2M9, Canada.
Baba
Tsukasa
T
Lee
Paula S
PS
Barnett
Jason C
JC
Sfakianos
Gregory P
GP
Secord
Angeles Alvarez
AA
Murphy
Susan K
SK
Iversen
Edwin
E
Marks
Jeffrey R
JR
Berchuck
Andrew
A
D000465:Algorithms; D016000:Cluster Analysis; D004252:DNA Mutational Analysis; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009154:Mutation; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis; D017741:Survivors; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53