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 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.
Wolf
Maija
M
Medical Biotechnology, VTT Technical Research Centre of Finland and University of Turku, FIN-20520 Turku, Finland. maija.wolf@vtt.fi
Edgren
Henrik
H
Muggerud
Aslaug
A
Kilpinen
Sami
S
Huusko
Pia
P
Sørlie
Therese
T
Mousses
Spyro
S
Kallioniemi
Olli
O
D000818:Animals; D045744:Cell Line, Tumor / Q000187:drug effects; D018389:Codon, Nonsense; D004640:Emetine / Q000494:pharmacology; D005820:Genetic Testing; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D011471:Prostatic Neoplasms; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D020871:RNA Stability / Q000187:drug effects; D012334:RNA, Neoplasm / Q000032:analysis; D036183:Receptor, EphB2 / Q000032:analysis / Q000235:genetics
D018389:Codon, Nonsense; D011500:Protein Synthesis Inhibitors; D012334:RNA, Neoplasm; D036183:Receptor, EphB2; D004640:Emetine