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Genitourinary tumours, prostate

4649 - DNA repair gene panel mutations in young onset and aggressive v non aggressive prostate cancer cases in the UK


10 Sep 2017


Genitourinary tumours, prostate


Translational Research;  Prostate Cancer


Ros Eeles


Annals of Oncology (2017) 28 (suppl_5): v269-v294. 10.1093/annonc/mdx370


R. Eeles1, E. Saunders1, S. Wakerell1, I. Whitmore1, C. Cieza-Borrella1, K. Govindasami1, T. Dadaev1, Z. Kote-Jarai1, D. Leongamornlert2

Author affiliations

  • 1 Genetics & Epidemiology, The Institute of Cancer Research, SM2 5NG - Sutton/GB
  • 2 Cancer, Ageing & Somatic Mutations Programme, Wellcome Trust Sanger Institute, Cambridge/GB


Abstract 4649


Prostate cancer (PrCa) is the most common solid tumour in men in the Western world. There is evidence that PrCa predisposition is due to germline common and rare variation.


We sequenced 175 genes in the DNA damage response and repair pathways using an Agilent custom capture kit and Illumina technology in PrCa cases diagnosed at 


We identified 5,118 single nucleotide variants (SNVs) and 172 indels; 216 unique protein truncating variants (PTVs) were in 96 genes of the 175 gene panel. The total number of PTVs in cases was significantly higher (181) than in controls (122); in particular, in the BROCA gene set of 22 tumour suppressor genes (P = 0.002). Mutations in BRCA1, BRCA2, ATM, MSH5 and CHEK2 were 3 times more common in cases compared with controls (P = 0.0018). To investigate if aggressive cases had a different mutation burden we compared 204 aggressive (Gleason score>8) versus 1049 non-aggressive (Gleason score ≤7) cases. In the single variant analysis, one variant in BRCA2, rs28897754 (K2950N) showed association with a more aggressive phenotype (P = 0.0016). Gene burden testing showed BRCA2, MSH2, PALB2 and CHEK2 had an OR > 3 in aggressive v non aggressive cases (14% v 4% respectively). Men who died of PrCa had a 17% incidence of mutation in a subset of the 175 gene panel.


We have shown that there is a higher percentage of DNA damage response and repair gene germline mutations in PrCa cases occurring at 

Clinical trial identification

UKGPCS - CCR0848 & 06/MRE02/4

Legal entity responsible for the study

The Institute of Cancer Research




All authors have declared no conflicts of interest.

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