NMD Microarray Analysis for Rapid Genome-Wide Screen of Mutated Genes in Cancer

Gene mutations play a critical role in cancer development and progression, and their identification offers possibilities for accurate diagnostics and therapeutic targeting. Finding genes undergoing mutations is challenging and slow, even in the post-genomic era. A new approach was recently developed...

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Bibliographic Details
Main Authors: Maija Wolf, Henrik Edgren, Aslaug Muggerud, Sami Kilpinen, Pia Huusko, Therese Sørlie, Spyro Mousses, Olli Kallioniemi
Format: Article
Language:English
Published: Hindawi Limited 2005-01-01
Series:Cellular Oncology
Online Access:http://dx.doi.org/10.1155/2005/478316
Description
Summary:Gene mutations play a critical role in cancer development and progression, and their identification offers possibilities for accurate diagnostics and therapeutic targeting. Finding genes undergoing mutations is challenging and slow, even in the post-genomic era. A new approach was recently developed by Noensie and Dietz to prioritize and focus the search, making use of nonsense-mediated mRNA decay (NMD) inhibition and microarray analysis (NMD microarrays) in the identification of transcripts containing nonsense mutations. We combined NMD microarrays with array-based CGH (comparative genomic hybridization) in order to identify inactivation of tumor suppressor genes in cancer. Such a “mutatomics” screening of prostate cancer cell lines led to the identification of inactivating mutations in the EPHB2 gene. Up to 8% of metastatic uncultured prostate cancers also showed mutations of this gene whose loss of function may confer loss of tissue architecture. NMD microarray analysis could turn out to be a powerful research method to identify novel mutated genes in cancer cell lines, providing targets that could then be further investigated for their clinical relevance and therapeutic potential.
ISSN:1570-5870
1875-8606