Identification of ARHGEF17, DENND2D, FGFR3, and RBI mutations in melanoma by inhibition of nonsense-mediated mRNA decay

Bloethner, Sandra, Mould, Arne, Stark, Mitchell and Hayward, Nicholas K. (2008) Identification of ARHGEF17, DENND2D, FGFR3, and RBI mutations in melanoma by inhibition of nonsense-mediated mRNA decay. Genes, Chromosomes and Cancer, 47 12: 1076-1085. doi:10.1002/gcc.20598


Author Bloethner, Sandra
Mould, Arne
Stark, Mitchell
Hayward, Nicholas K.
Title Identification of ARHGEF17, DENND2D, FGFR3, and RBI mutations in melanoma by inhibition of nonsense-mediated mRNA decay
Journal name Genes, Chromosomes and Cancer   Check publisher's open access policy
ISSN 1045-2257
Publication date 2008-12-01
Year available 2008
Sub-type Article (original research)
DOI 10.1002/gcc.20598
Open Access Status
Volume 47
Issue 12
Start page 1076
End page 1085
Total pages 10
Editor F. Mitelman
J. D. Rowley
Place of publication United States
Publisher John Wiley & Sons, Inc.
Language eng
Subject C1
970111 Expanding Knowledge in the Medical and Health Sciences
111203 Cancer Genetics
111201 Cancer Cell Biology
Abstract 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. © 2008 Wiley-Liss, Inc.
Keyword Oncology
Genetics & Heredity
Oncology
Genetics & Heredity
GENETICS & HEREDITY
ONCOLOGY
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Wed, 15 Apr 2009, 21:14:07 EST by Amanda Jones on behalf of Medicine - Royal Brisbane and Women's Hospital