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

A Letessier; S Garrido-Urbani; C Ginestier; G Fournier; B Esterni; F Monville; J Adélaïde; J Geneix; L Xerri; P Dubreuil; P Viens; E Charafe-Jauffret; J Jacquemier; D Birnbaum; M Lopez; M Chaffanet

doi:10.1038/sj.onc.1209772

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

Oncogene. 2007 Jan 11;26(2):298-307. doi: 10.1038/sj.onc.1209772. Epub 2006 Jul 3.

Authors

A Letessier¹, S Garrido-Urbani, C Ginestier, G Fournier, B Esterni, F Monville, J Adélaïde, J Geneix, L Xerri, P Dubreuil, P Viens, E Charafe-Jauffret, J Jacquemier, D Birnbaum, M Lopez, M Chaffanet

Affiliation

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

PMID: 16819513
DOI: 10.1038/sj.onc.1209772

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acid Anhydride Hydrolases / genetics*
Acid Anhydride Hydrolases / metabolism
Adult
Aged
Aged, 80 and over
Blotting, Western
Breast Neoplasms / diagnosis
Breast Neoplasms / genetics*
Breast Neoplasms / metabolism
Carcinoma, Ductal, Breast / diagnosis
Carcinoma, Ductal, Breast / genetics
Carcinoma, Ductal, Breast / metabolism
Carcinoma, Lobular / diagnosis
Carcinoma, Lobular / genetics
Carcinoma, Lobular / metabolism
Chromosome Breakage*
Chromosome Fragile Sites
Chromosomes, Human, Pair 6 / genetics
Female
Fluorescent Antibody Technique
Genes, Tumor Suppressor
Humans
Immunoenzyme Techniques
In Situ Hybridization, Fluorescence
Kinesins / genetics*
Kinesins / metabolism
MicroRNAs
Middle Aged
Myosins / genetics*
Myosins / metabolism
Neoplasm Invasiveness / pathology
Neoplasm Proteins / genetics*
Neoplasm Proteins / metabolism
Prognosis
RNA Interference
Survival Rate
Tissue Array Analysis
Ubiquitin-Protein Ligases / genetics*
Ubiquitin-Protein Ligases / metabolism

Substances

AFDN protein, human
MicroRNAs
Neoplasm Proteins
fragile histidine triad protein
Ubiquitin-Protein Ligases
parkin protein
Acid Anhydride Hydrolases
Myosins
Kinesins