Expression signatures of TP53 mutations in serous ovarian cancers.

Bernardini, Marcus Q

Baba, Tsukasa

Lee, Paula S

Barnett, Jason C

Sfakianos, Gregory P

Secord, Angeles Alvarez

Murphy, Susan K

Iversen, Edwin

Marks, Jeffrey R

Berchuck, Andrew

England

2011-06-21T17:29:35Z

2010-05-26

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.

Version of Record

http://www.ncbi.nlm.nih.gov/pubmed/20504346

1471-2407-10-237

1471-2407

https://hdl.handle.net/10161/4356

eng

en_US

Springer Science and Business Media LLC

BMC Cancer

10.1186/1471-2407-10-237

Bmc Cancer

Algorithms

Cluster Analysis

DNA Mutational Analysis

Female

Gene Expression Profiling

Gene Expression Regulation, Neoplastic

Humans

Mutation

Neoplasm Staging

Oligonucleotide Array Sequence Analysis

Ovarian Neoplasms

Prognosis

Survival Analysis

Survivors

Time Factors

Tumor Suppressor Protein p53

Expression signatures of TP53 mutations in serous ovarian cancers.

Journal article

Murphy, Susan K|0000-0001-8298-7272

Marks, Jeffrey R|0000-0002-2054-5468

2010-5-26

10

http://www.ncbi.nlm.nih.gov/pubmed/20504346

237

Clinical Science Departments

Duke

Duke Cancer Institute

Institutes and Centers

Obstetrics and Gynecology

Obstetrics and Gynecology, Gynecologic Oncology

Pathology

School of Medicine

Statistical Science

Surgery

Surgery, Surgical Sciences

Trinity College of Arts & Sciences

Published online

10