Expression signatures of TP53 mutations in serous ovarian cancers

BMC Cancer

Research Article

Andrew Berchuck¹  Gregory P Sfakianos¹  Susan K Murphy¹  Tsukasa Baba¹  Paula S Lee¹  Angeles Alvarez Secord¹  Jason C Barnett¹  Marcus Q Bernardini²  Edwin Iversen³  Jeffrey R Marks⁴ 

[1] Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Duke University Medical Center, 27708, Durham, NC, USA;Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Toronto, 600 University Avenue, M5G 2M9, Toronto, Ontario, Canada;Department of Statistical Science, Duke University, 27708, Durham, NC, USA;Department of Surgery, Duke University Medical Center, 27708, Durham, NC, USA;

关键词: Ovarian Cancer;    Epithelial Ovarian Cancer;    Null Mutation;    TP53 Mutation;    Early Stage Cancer;   

DOI  :  10.1186/1471-2407-10-237

 received in 2009-08-05, accepted in 2010-05-26,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundMutations 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.MethodsThe 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.ResultsMissense 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.ConclusionsThis 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.

【 授权许可】

Unknown   
© Bernardini et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.