Affiliations: Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, FIN-20520 Turku, Finland | Department of Genetics, The Norwegian Radium Hospital, N-0310 Oslo, Norway | Translational Genomics Research Institute, Gaithersburg, MD 20878-1762, USA
Note: [] Corresponding author: Maija Wolf, Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, Itäinen Pitkäkatu 4, FIN-20520 Turku, Finland. Tel.: +358 9 471 71916; Fax: +358 9 471 71731; E-mail: [email protected].
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.
