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

Pia Huusko, 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 OzcelikSabine Elowe, Tony Pawson, Jeffrey M. Trent, John D. Carpten, Olli Kallioniemi, Spyro Mousses

Research output: Contribution to journalArticleScientificpeer-review

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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.
Original languageEnglish
Pages (from-to)979-983
JournalNature Genetics
Volume36
Issue number9
DOIs
Publication statusPublished - 2004
MoE publication typeA1 Journal article-refereed

Fingerprint

Microarray Analysis
Prostatic Neoplasms
Nonsense Codon
Mutation
Alleles
Neoplasm Metastasis
Comparative Genomic Hybridization
RNA Stability
Receptor Protein-Tyrosine Kinases
Missense Mutation
Tumor Suppressor Genes
Genes
Cell Movement
Transfection
Neoplasms
Maintenance
Genome
Cell Line
Brain
Growth

Keywords

  • microarray
  • cDNA microarrays
  • RNA decay microarrays
  • tyrosine kinase
  • tumor suppressor gene

Cite this

Huusko, P., Ponciano-Jackson, D., Wolf, M., Kiefer, J. A., Azorsa, D. O., Tuzmen, S., ... Mousses, S. (2004). Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer. Nature Genetics, 36(9), 979-983. https://doi.org/10.1038/ng1408
Huusko, Pia ; Ponciano-Jackson, Damaris ; Wolf, Maija ; Kiefer, Jeff A. ; Azorsa, David O. ; Tuzmen, Sukru ; Weaver, Don ; Robbins, Christiane ; Moses, Tracy ; Allinen, Minna ; Hautaniemi, Sampsa ; Chen, Yidong ; Elkahloun, Abdel ; Basik, Mark ; Bova, G. Steven ; Bubendorf, Lukas ; Lugli, Alessandro ; Sauter, Guido ; Schleutker, Johanna ; Ozcelik, Hilmi ; Elowe, Sabine ; Pawson, Tony ; Trent, Jeffrey M. ; Carpten, John D. ; Kallioniemi, Olli ; Mousses, Spyro. / Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer. In: Nature Genetics. 2004 ; Vol. 36, No. 9. pp. 979-983.
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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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Huusko, P, Ponciano-Jackson, D, Wolf, M, Kiefer, JA, Azorsa, DO, Tuzmen, S, Weaver, D, Robbins, C, Moses, T, Allinen, M, Hautaniemi, S, Chen, Y, Elkahloun, A, Basik, M, Bova, GS, Bubendorf, L, Lugli, A, Sauter, G, Schleutker, J, Ozcelik, H, Elowe, S, Pawson, T, Trent, JM, Carpten, JD, Kallioniemi, O & Mousses, S 2004, 'Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer', Nature Genetics, vol. 36, no. 9, pp. 979-983. https://doi.org/10.1038/ng1408

Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer. / Huusko, Pia; Ponciano-Jackson, Damaris; Wolf, Maija; Kiefer, Jeff A.; Azorsa, David O.; Tuzmen, Sukru; Weaver, Don; Robbins, Christiane; Moses, Tracy; Allinen, Minna; Hautaniemi, Sampsa; Chen, Yidong; Elkahloun, Abdel; Basik, Mark; Bova, G. Steven; Bubendorf, Lukas; Lugli, Alessandro; Sauter, Guido; Schleutker, Johanna; Ozcelik, Hilmi; Elowe, Sabine; Pawson, Tony; Trent, Jeffrey M.; Carpten, John D.; Kallioniemi, Olli (Corresponding Author); Mousses, Spyro (Corresponding Author).

In: Nature Genetics, Vol. 36, No. 9, 2004, p. 979-983.

Research output: Contribution to journalArticleScientificpeer-review

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T1 - Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer

AU - Huusko, Pia

AU - Ponciano-Jackson, Damaris

AU - Wolf, Maija

AU - Kiefer, Jeff A.

AU - Azorsa, David O.

AU - Tuzmen, Sukru

AU - Weaver, Don

AU - Robbins, Christiane

AU - Moses, Tracy

AU - Allinen, Minna

AU - Hautaniemi, Sampsa

AU - Chen, Yidong

AU - Elkahloun, Abdel

AU - Basik, Mark

AU - Bova, G. Steven

AU - Bubendorf, Lukas

AU - Lugli, Alessandro

AU - Sauter, Guido

AU - Schleutker, Johanna

AU - Ozcelik, Hilmi

AU - Elowe, Sabine

AU - Pawson, Tony

AU - Trent, Jeffrey M.

AU - Carpten, John D.

AU - Kallioniemi, Olli

AU - Mousses, Spyro

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AB - 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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KW - tumor suppressor gene

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DO - 10.1038/ng1408

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Huusko P, Ponciano-Jackson D, Wolf M, Kiefer JA, Azorsa DO, Tuzmen S et al. Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 in human prostate cancer. Nature Genetics. 2004;36(9):979-983. https://doi.org/10.1038/ng1408