Linked Life Data

18677770

Source:http://linkedlifedata.com/resource/pubmed/id/18677770

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2008-10-13
pubmed:abstractText
Gene identification by nonsense-mediated mRNA decay inhibition (GINI) has proven to be a strategy for genome-wide discovery of genes containing inactivating mutations in colon and prostate cancers. Here, we present the first study of inhibition of the nonsense-mediated mRNA decay (NMD) pathway in melanoma. We used a combination of emetine and actinomycin D treatment to stabilize mRNAs containing premature termination codons (PTCs), followed by microarray analysis and sequencing to identify novel tumor suppressor genes (TSGs) in a panel of 12 melanoma cell lines. Stringent analysis of the array data was used to select 35 candidate genes for sequencing. Of these, 4 (11%) were found to carry PTCs, including ARHGEF17, DENND2D, FGFR3, and RB1. While RB1 mutations have previously been described in melanoma, the other three genes represent potentially novel melanoma; TSGs. ARHGEF17 showed a G1865A mutation leading to W622X in a cell line derived from a mucosal melanoma; in RB1 a C1411T base change resulting in Q471X was discovered in a cell line derived from an acral melanoma; and the FGFR3 and DENND2D genes had intronic insertions leading to PTCs in cell lines derived from superficially spreading melanomas. We conclude that although the false positive rate is high, most likely due to the lack of DNA mismatch repair gene defects, the GINI protocol is one approach to discover novel TSGs in melanoma.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1098-2264
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1076-85
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Identification of ARHGEF17, DENND2D, FGFR3, and RB1 mutations in melanoma by inhibition of nonsense-mediated mRNA decay.
pubmed:affiliation
Queensland Institute of Medical Research, 300 Herston Rd, Herston, QLD 4029, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't