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...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2010-05-01
|
Series: | BMC Cancer |
Online Access: | http://www.biomedcentral.com/1471-2407/10/237 |
_version_ | 1811297761572683776 |
---|---|
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> |
first_indexed | 2024-04-13T06:08:59Z |
format | Article |
id | doaj.art-a0c10033760e4b99b4c5a4089c5e430c |
institution | Directory Open Access Journal |
issn | 1471-2407 |
language | English |
last_indexed | 2024-04-13T06:08:59Z |
publishDate | 2010-05-01 |
publisher | BMC |
record_format | Article |
series | BMC Cancer |
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 |
work_keys_str_mv | AT murphysusank expressionsignaturesofittp53itmutationsinserousovariancancers AT secordangeles expressionsignaturesofittp53itmutationsinserousovariancancers AT sfakianosgregoryp expressionsignaturesofittp53itmutationsinserousovariancancers AT barnettjasonc expressionsignaturesofittp53itmutationsinserousovariancancers AT leepaulas expressionsignaturesofittp53itmutationsinserousovariancancers AT babatsukasa expressionsignaturesofittp53itmutationsinserousovariancancers AT bernardinimarcusq expressionsignaturesofittp53itmutationsinserousovariancancers AT iversenedwin expressionsignaturesofittp53itmutationsinserousovariancancers AT marksjeffreyr expressionsignaturesofittp53itmutationsinserousovariancancers AT berchuckandrew expressionsignaturesofittp53itmutationsinserousovariancancers |