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Analysis of genetic and epigenetic processes that influence p14ARF expression in breast cancer

Oncogene volume 20, pages 4586–4590 (2001)Cite this article

Abstract

The INK4a/ARF locus encodes two unrelated cell cycle-regulatory proteins that both function in tumor suppression, p16INK4a and p14ARF. In human tumors including breast cancer, alterations affecting selectively p14ARF have been poorly analysed. We have performed a comprehensive analysis of the inactivation mechanisms (mutation, homozygous and hemizygous deletion, and promoter hypermethylation) in a large series of 100 primary breast carcinomas. RT–PCR showed expression variable of the p14ARF transcript, with 17% demonstrating overexpression and 26% demonstrating decreased expression. No detectable alterations were observed in the majority of cases with overexpressed p14ARF mRNA, but 77% of tumors with decreased expression presented at least one of these genetic/epigenetic alterations. Nevertheless, a statistically significant correlation was observed between decreased p14ARF expression and several poor prognostic parameters.

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Acknowledgements

We are grateful to Mr Robin Rycroft for his assistance with the English language, revision and preparation of the manuscript. This work was supported by grants from the Fundación Banco Santander Central Hispano, Aventis Pharma S.A and CAM 08.1/0069/20002.

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Authors and Affiliations

  1. Department of Medical Oncology, Clínica Puerta de Hierro, E-28035, Madrid, Spain

    Javier Silva, Gemma Domínguez, José M Silva, Jose M García, Mariano Provencio, Pilar España & Félix Bonilla

  2. Department of Pathology, Clínica Puerta de Hierro, E-28035, Madrid

    César Corbacho

  3. Department of Pathology, Hospital Santa Cristina, E-28009, Madrid, Spain

    Isabel Gallego

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  1. Javier Silva
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Silva, J., Domínguez, G., Silva, J. et al. Analysis of genetic and epigenetic processes that influence p14ARF expression in breast cancer. Oncogene 20, 4586–4590 (2001). https://doi.org/10.1038/sj.onc.1204617

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