Table of Contents Author Guidelines Submit a Manuscript
Cellular Oncology
Volume 27, Issue 3, Pages 169-173
http://dx.doi.org/10.1155/2005/478316
Review

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

Maija Wolf,1 Henrik Edgren,1 Aslaug Muggerud,2 Sami Kilpinen,1 Pia Huusko,3 Therese Sørlie,2 Spyro Mousses,3 and Olli Kallioniemi1

1Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, FIN-20520 Turku, Finland
2Department of Genetics, The Norwegian Radium Hospital, N-0310 Oslo, Norway
3Translational Genomics Research Institute, Gaithersburg, MD 20878-1762, USA

Copyright © 2005 Hindawi Publishing Corporation and the authors. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.