Page 15 - Flipbook

DNA Response Defects in mCRPC

Multiple pathways have been identified with genomic • mCRPC patients (N = 150)

alterations in association with advanced prostate cancer

• 22.7% (34/150) had DNA response alterations,

many of which were biallelic

• 19/150 (12.7%) with loss of BRCA2

• ~ 90% were biallelic, with 8/150 (5.3%) resulting
from a pathogenic germline BRCA2 mutation + a

somatic event
Tumour/
germline
exomes
• Recurrent biallelic loss of ATM also observed,
including some arising from pathogenic germline

alterations

• Mutation events also observed in BRCA1, CDK12,

FANCA, RAD51B, and RAD51C
Monoallelic: An alteration in one copy of a gene with one remaining normal copy
Biallelic: An alteration in both copies of a gene; the mutation in each allele may not be the same

mCRPC, metastatic castration resistant prostate cancer
Robinson D et al. Cell 2015;5:1215-28.