CHD1 is a 5q21 tumor suppressor required for ERG rearrangement in prostate cancer
A partir de 2 093 échantillons tumoraux prélevés sur des patients atteints d'un cancer de la prostate, puis menée in vitro, cette étude met en évidence le rôle de suppresseur de tumeurs joué par le gène CHD1, localisé sur la région chromosomique 5q21
Deletions involving the chromosomal band 5q21 are among the most frequent alterations in prostate cancer. Using SNP arrays, we mapped a 1.3 megabase minimally deleted region including only the RGMB and CHD1 genes. Functional analyses demonstrated that CHD1 is an essential tumor suppressor. FISH analysis of 2,093 prostate cancers revealed a strong association between CHD1 deletion, PSA biochemical failure (p=0.0038) and absence of ERG fusion (p<0.0001). We found that inactivation of CHD1 in vitro prevents formation of ERG rearrangements due to impairment of AR-dependent transcription, a prerequisite for ERG translocation. CHD1 is required for efficient recruitment of AR to responsive promoters, and regulates expression of known AR-responsive tumor suppressor genes including NKX3-1, FOXO1 and PPARγ. Our study establishes CHD1 as the 5q21 tumor suppressor gene in prostate cancer and demonstrates a key role of this chromatin remodeling factor in prostate cancer biology.