Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Genitourinary tumours, prostate

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

Date

10 Sep 2017

Session

Genitourinary tumours, prostate

Topics

Translational Research;  Prostate Cancer

Presenters

Ros Eeles

Citation

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

Authors

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
More

Resources

Abstract 4649

Background

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.

Methods

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 

Results

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.

Conclusions

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

Funding

None

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.