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CHD1 Deletion: Implications to Outcome and Treatment in Prostate Cancer (CDELP)
Date du début: 4 avr. 2014, Date de fin: 3 avr. 2016 PROJET  TERMINÉ 

Prostate cancer can be stratified as ETS gene rearranged (ETSR) andnon-rearranged (ETSNR), with the latter comprising a heterogeneousgroup of 50-60% of all cancers. This project will characterize a subgroupof ETSNR cancers that have a CHD1 deletion (CHD1del). Recentsequencing studies have elucidated CHD1- cancers as ETSNR, andcommonly PTEN and p53 wildtype and SPOP mutated, comprising up to26% of all prostate cancers (1). ETSR cancers largely have hormonedriven oncogenes that may have prognostic and predictive utility (2, 3).Less is known about ETSNRCHD1del cancers. Their lack of ETS fusionsraises concern that these may not be generated through androgenreceptor (AR) transcription and are not AR driven. ETSNRCHD1del cancershave a huge excess of somatic intrachromosomal rearrangements (up to800) compared to ETSR cancers presumably due to a DNA repair defect(1). This is supported by CHD1’s association with the SSRP1, part of theFACT complex, that is implicated in transcriptional regulation and DNArepair (4-9). We hypothesize that CHD1 deleted tumors are lesssensitive to endocrine and taxane therapy, have a worse prognosisand need alternative treatment strategies.