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Expression changes of the MAD mitotic checkpoint gene family in renal cell carcinomas characterized by numerical chromosome changes

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Abstract

Papillary and chromophobe renal cell carcinomas are characterized by multiple trisomies and monosomies, respectively, but the molecular mechanisms behind the acquisition of these numerical chromosome changes are unknown. To evaluate the role of mitotic checkpoint defects for the karyotypic patterns characteristic of these two renal cell cancer subtypes, we analyzed the messenger RNA expression levels of the major mitotic checkpoint genes of the budding uninhibited by benzimidazole family (BUB1, BUBR1, BUB3) and of the mitotic arrest deficiency family (MAD1, MAD2L1, MAD2L2) by real-time quantitative polymerase chain reaction in 30 renal cell cancer samples (11 chromophobe and 19 papillary) and 36 normal kidney tissue samples. MAD1, MAD2L1, and MAD2L2 showed significant expression differences in tumor tissue compared to controls. Chromophobe tumors presented underexpression of MAD1, and MAD2L2, whereas papillary tumors showed overexpression of MAD2L1. The expression level of the BUB gene family did not differ significantly from that of normal kidney. We conclude that expression changes in mitotic arrest deficiency genes (MAD1, MAD2L1, and MAD2L2) play a role in renal carcinogenesis characterized by multiple numerical chromosome abnormalities.

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Acknowledgments

This study was supported by the Fundação para a Ciência e a Tecnologia (FCT; Projecto de Investigação Plurianual do Centro de Investigação do IPO-Porto [03-05]). FRR (grant SFRH/BD7067/2001) and MP (grant SFRH/BPD/14506/2003) are research fellows of FCT.

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Authors and Affiliations

  1. Department of Genetics, Portuguese Oncology Institute, Rua Dr António Bernardino de Almeida, 4200-072,, Porto, Portugal

    Mafalda Pinto, Maria J. Soares, Nuno Cerveira, Franclim R. Ribeiro, Carmen Jerónimo & Manuel R. Teixeira

  2. Department of Pathology, Portuguese Oncology Institute, Rua Dr António Bernardino de Almeida, 4200-072,, Porto, Portugal

    Rui Henrique

  3. Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto, Largo Professor Abel Salazar, 2-4099-003,, Porto, Portugal

    Rui Henrique, Carmen Jerónimo & Manuel R. Teixeira

  4. Department of Urology, Portuguese Oncology Institute, Rua Dr António Bernardino de Almeida, 4200-072,, Porto, Portugal

    Jorge Oliveira

  5. Fernando Pessoa University School of Health Sciences, Rua Carlos da Maia, 296-4200-150,, Porto, Portugal

    Carmen Jerónimo

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  1. Mafalda Pinto
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  2. Maria J. Soares
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Correspondence to Manuel R. Teixeira.

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Pinto, M., Soares, M.J., Cerveira, N. et al. Expression changes of the MAD mitotic checkpoint gene family in renal cell carcinomas characterized by numerical chromosome changes. Virchows Arch 450, 379–385 (2007). https://doi.org/10.1007/s00428-007-0386-7

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  • DOI: https://doi.org/10.1007/s00428-007-0386-7

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