Linked Life Data

20663929

Source:http://linkedlifedata.com/resource/pubmed/id/20663929

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2010-8-11
pubmed:abstractText
By high-throughput screens of somatic mutations of genes in cancer genomes, hundreds of cancer genes are being rapidly identified, providing us abundant information for systematically deciphering the genetic changes underlying cancer mechanism. However, the functional collaboration of mutated genes is often neglected in current studies. Here, using four genome-wide somatic mutation data sets and pathways defined in various databases, we showed that gene pairs significantly comutated in cancer samples tend to distribute between pathways rather than within pathways. At the basic functional level of motifs in the human protein-protein interaction network, we also found that comutated gene pairs were overrepresented between motifs but extremely depleted within motifs. Specifically, we showed that based on Gene Ontology that describes gene functions at various specific levels, we could tackle the pathway definition problem to some degree and study the functional collaboration of gene mutations in cancer genomes more efficiently. Then, by defining pairs of pathways frequently linked by comutated gene pairs as the between-pathway models, we showed they are also likely to be codisrupted by mutations of the interpathway hubs of the coupled pathways, suggesting new hints for understanding the heterogeneous mechanisms of cancers. Finally, we showed some between-pathway models consisting of important pathways such as cell cycle checkpoint and cell proliferation were codisrupted in most cancer samples under this study, suggesting that their codisruptions might be functionally essential in inducing these cancers. All together, our results would provide a channel to detangle the complex collaboration of the molecular processes underlying cancer mechanism.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1538-8514
pubmed:author
pubmed:copyrightInfo
(c) 2010 AACR.
pubmed:issnType
Electronic
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2186-95
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Systematic interpretation of comutated genes in large-scale cancer mutation profiles.
pubmed:affiliation
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't