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Content archived on 2024-05-30

CHD1 Deletion: Implications to Outcome and Treatment in Prostate Cancer

Objective

Prostate cancer can be stratified as ETS gene rearranged (ETSR) and
non-rearranged (ETSNR), with the latter comprising a heterogeneous
group of 50-60% of all cancers. This project will characterize a subgroup
of ETSNR cancers that have a CHD1 deletion (CHD1del). Recent
sequencing studies have elucidated CHD1- cancers as ETSNR, and
commonly PTEN and p53 wildtype and SPOP mutated, comprising up to
26% of all prostate cancers (1). ETSR cancers largely have hormone
driven oncogenes that may have prognostic and predictive utility (2, 3).
Less is known about ETSNRCHD1del cancers. Their lack of ETS fusions
raises concern that these may not be generated through androgen
receptor (AR) transcription and are not AR driven. ETSNRCHD1del cancers
have a huge excess of somatic intrachromosomal rearrangements (up to
800) compared to ETSR cancers presumably due to a DNA repair defect
(1). This is supported by CHD1’s association with the SSRP1, part of the
FACT complex, that is implicated in transcriptional regulation and DNA
repair (4-9). We hypothesize that CHD1 deleted tumors are less
sensitive to endocrine and taxane therapy, have a worse prognosis
and need alternative treatment strategies.

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Topic(s)

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Call for proposal

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FP7-PEOPLE-2013-IIF
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Funding Scheme

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MC-IIF - International Incoming Fellowships (IIF)

Coordinator

INSTITUTE OF CANCER RESEARCH: THE ROYAL CANCER HOSPITAL LBG
EU contribution
€ 231 283,20
Address
OLD BROMPTON ROAD 123
SW7 3RP London
United Kingdom

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Region
London Inner London — West Kensington & Chelsea and Hammersmith & Fulham
Activity type
Higher or Secondary Education Establishments
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Total cost

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