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  • Oncogenomics
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Correlated break at PARK2/FRA6E and loss of AF-6/Afadin protein expression are associated with poor outcome in breast cancer

Oncogene volume 26, pages 298–307 (2007)Cite this article

Abstract

Common fragile sites (CFSs) are regions of chromosomal break that may play a role in oncogenesis. The most frequent alteration occurs at FRA3B, within the FHIT gene, at chromosomal region 3p14. We studied a series of breast carcinomas for break of a CFS at 6q26, FRA6E, and its associated gene PARK2, using fluorescence in situ hybridization on tissue microarrays (TMA). We found break of PARK2 in 6% of cases. We studied the PARK2-encoded protein Parkin by using immunohistochemistry on the same TMA. Loss of Parkin was found in 13% of samples but was not correlated with PARK2 break. PARK2 break but not Parkin expression was correlated with prognosis. Alteration of PARK2/FRA6E may cause haplo-insufficiency of one or several telomeric potential tumor suppressor genes (TSG). The AF-6/MLLT4 gene, telomeric of PARK2, encodes the Afadin scaffold protein, which is essential for epithelial integrity. Loss of Afadin was found in 14.5% of cases, and 36% of these cases showed PARK2 break. Loss of Afadin had prognostic impact, suggesting that AF-6 may be a TSG. Loss of Afadin was correlated with loss of FHIT expression, suggesting fragility of FRA6E and FRA3B in a certain proportion of breast tumors.

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Acknowledgements

We thank F Birg and D Maraninchi for encouragements, C Chabannon for biobank sample management and JM Durey for his help with iconography. This work was supported by Institut Paoli-Calmettes, INSERM, and grants from Ligue Nationale Contre le Cancer (LNCC) (Label 2003-2006), the Association pour la Recherche contre le Cancer (ARC-3128) and Ministries of Health and Research (Cancéropôle PACA). SGU, CG and FM are supported by a fellowship from Ministry of Research and AL by a fellowship from LNCC.

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Author notes

  1. A Letessier and S Garrido-Urbani: These authors contributed equally to this work.

Authors and Affiliations

  1. Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, UMR599 Inserm et Institut Paoli-Calmettes, Marseille, France

    A Letessier, C Ginestier, F Monville, J Adélaïde, J Geneix, E Charafe-Jauffret, J Jacquemier, D Birnbaum & M Chaffanet

  2. Hématopoièse Fonctionnelle et Moléculaire, UMR599 Inserm et Institut Paoli-Calmettes, Marseille, France

    S Garrido-Urbani, G Fournier, P Dubreuil & M Lopez

  3. Département de Biostatistiques, Institut Paoli-Calmettes, Marseille, France

    B Esterni

  4. Département d'Oncologie Médicale, UMR599 Inserm et Institut Paoli-Calmettes, Marseille, France

    B Esterni & P Viens

  5. Département de BioPathologie, Institut Paoli-Calmettes, Marseille, France

    L Xerri, E Charafe-Jauffret & J Jacquemier

  6. Faculté de Médecine, Université de la Méditerranée, Marseille, France

    L Xerri, P Viens & E Charafe-Jauffret

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  1. A Letessier
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Correspondence to D Birnbaum.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Letessier, A., Garrido-Urbani, S., Ginestier, C. et al. Correlated break at PARK2/FRA6E and loss of AF-6/Afadin protein expression are associated with poor outcome in breast cancer. Oncogene 26, 298–307 (2007). https://doi.org/10.1038/sj.onc.1209772

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