Expression signatures of <it>TP53 </it>mutations in serous ovarian cancers

<p>Abstract</p> <p>Background</p> <p>Mutations in the <it>TP53 </it>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 a...

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Main Authors: Murphy Susan K, Secord Angeles, Sfakianos Gregory P, Barnett Jason C, Lee Paula S, Baba Tsukasa, Bernardini Marcus Q, Iversen Edwin, Marks Jeffrey R, Berchuck Andrew
Format: Article
Language:English
Published: BMC 2010-05-01
Series:BMC Cancer
Online Access:http://www.biomedcentral.com/1471-2407/10/237
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author Murphy Susan K
Secord Angeles
Sfakianos Gregory P
Barnett Jason C
Lee Paula S
Baba Tsukasa
Bernardini Marcus Q
Iversen Edwin
Marks Jeffrey R
Berchuck Andrew
author_facet Murphy Susan K
Secord Angeles
Sfakianos Gregory P
Barnett Jason C
Lee Paula S
Baba Tsukasa
Bernardini Marcus Q
Iversen Edwin
Marks Jeffrey R
Berchuck Andrew
author_sort Murphy Susan K
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Mutations in the <it>TP53 </it>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.</p> <p>Methods</p> <p>The <it>TP53 </it>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.</p> <p>Results</p> <p>Missense or chain terminating (null) mutations in <it>TP53 </it>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 <it>TP53 </it>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.</p> <p>Conclusions</p> <p>This represents the first attempt to define a genomic signature of <it>TP53 </it>mutation in ovarian cancer. Patterns of gene expression characteristic of <it>TP53 </it>mutation could be discerned and included several genes that are known p53 targets or have been described in the context of expression signatures of <it>TP53 </it>mutation in breast cancer.</p>
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spelling doaj.art-a0c10033760e4b99b4c5a4089c5e430c2022-12-22T02:59:08ZengBMCBMC Cancer1471-24072010-05-0110123710.1186/1471-2407-10-237Expression signatures of <it>TP53 </it>mutations in serous ovarian cancersMurphy Susan KSecord AngelesSfakianos Gregory PBarnett Jason CLee Paula SBaba TsukasaBernardini Marcus QIversen EdwinMarks Jeffrey RBerchuck Andrew<p>Abstract</p> <p>Background</p> <p>Mutations in the <it>TP53 </it>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.</p> <p>Methods</p> <p>The <it>TP53 </it>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.</p> <p>Results</p> <p>Missense or chain terminating (null) mutations in <it>TP53 </it>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 <it>TP53 </it>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.</p> <p>Conclusions</p> <p>This represents the first attempt to define a genomic signature of <it>TP53 </it>mutation in ovarian cancer. Patterns of gene expression characteristic of <it>TP53 </it>mutation could be discerned and included several genes that are known p53 targets or have been described in the context of expression signatures of <it>TP53 </it>mutation in breast cancer.</p>http://www.biomedcentral.com/1471-2407/10/237
spellingShingle Murphy Susan K
Secord Angeles
Sfakianos Gregory P
Barnett Jason C
Lee Paula S
Baba Tsukasa
Bernardini Marcus Q
Iversen Edwin
Marks Jeffrey R
Berchuck Andrew
Expression signatures of <it>TP53 </it>mutations in serous ovarian cancers
BMC Cancer
title Expression signatures of <it>TP53 </it>mutations in serous ovarian cancers
title_full Expression signatures of <it>TP53 </it>mutations in serous ovarian cancers
title_fullStr Expression signatures of <it>TP53 </it>mutations in serous ovarian cancers
title_full_unstemmed Expression signatures of <it>TP53 </it>mutations in serous ovarian cancers
title_short Expression signatures of <it>TP53 </it>mutations in serous ovarian cancers
title_sort expression signatures of it tp53 it mutations in serous ovarian cancers
url http://www.biomedcentral.com/1471-2407/10/237
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