Correlated break at PARK2/FRA6E and loss of AF-6/Afadin protein expression are associated with poor outcome in breast cancer - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Oncogene Année : 2007

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

D. Birnbaum
  • Fonction : Auteur
M. Chaffanet
S. Garrido-Urbani
  • Fonction : Auteur
G. Fournier
  • Fonction : Auteur
B. Esterni
  • Fonction : Auteur
F. Monville
  • Fonction : Auteur
José Adelaïde
  • Fonction : Auteur
  • PersonId : 897378
J. Geneix
  • Fonction : Auteur
L. Xerri
  • Fonction : Auteur
P. Dubreuil
  • Fonction : Auteur
P. Viens
  • Fonction : Auteur

Résumé

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.

Dates et versions

hal-01431963 , version 1 (11-01-2017)

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Citer

J. Jacquemier, D. Birnbaum, M. López, M. Chaffanet, A. Letessier, et al.. Correlated break at PARK2/FRA6E and loss of AF-6/Afadin protein expression are associated with poor outcome in breast cancer. Oncogene, 2007, 26 (2), pp.298-307. ⟨10.1038/sj.onc.1209772⟩. ⟨hal-01431963⟩
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