Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer

Nat Genet. 2004 Sep;36(9):979-83. doi: 10.1038/ng1408.

Pia Huusko ¹, Damaris Ponciano-Jackson, Maija Wolf, Jeff A Kiefer, David O Azorsa, Sukru Tuzmen, Don Weaver, Christiane Robbins, Tracy Moses, Minna Allinen, Sampsa Hautaniemi, Yidong Chen, Abdel Elkahloun, Mark Basik, G Steven Bova, Lukas Bubendorf, Alessandro Lugli, Guido Sauter, Johanna Schleutker, Hilmi Ozcelik, Sabine Elowe, Tony Pawson, Jeffrey M Trent, John D Carpten, Olli-P Kallioniemi, Spyro Mousses

Affiliations

Affiliation

1 Translational Genomics Research Institute, Cancer Drug Development Laboratory, 20 Firstfield Road, Suite 110, Gaithersburg, Maryland 20878, USA.

PMID: 15300251 DOI: 10.1038/ng1408

Abstract

The identification of tumor-suppressor genes in solid tumors by classical Cancer genetics methods is difficult and slow. We combined nonsense-mediated RNA decay microarrays and array-based comparative genomic hybridization for the genome-wide identification of genes with biallelic inactivation involving nonsense mutations and loss of the wild-type allele. This approach enabled us to identify previously unknown mutations in the receptor tyrosine kinase gene EphB2. The DU 145 prostate Cancer cell line, originating from a brain metastasis, carries a truncating mutation of EphB2 and a deletion of the remaining allele. Additional frameshift, splice site, missense and nonsense mutations are present in clinical prostate Cancer samples. Transfection of DU 145 cells, which lack functional EphB2, with wild-type EphB2 suppresses clonogenic growth. Taken together with studies indicating that EphB2 may have an essential role in cell migration and maintenance of normal tissue architecture, our findings suggest that mutational inactivation of EphB2 may be important in the progression and metastasis of prostate Cancer.

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