Page 14 - Flipbook

Metastatic Prostate Cancer is Biologically Heterogeneous

Approximately 25% of patients with mCRPC have alterations associated with DNA response pathways

AR
ETS
TP53
PTEN
RB1 • Multi-institutional study
PIK3CA
KMT2C • 444 tumours from 429 mCRPC patients
FOXA1
KMT2D
BRCA2 PI3K
APC • Single-nucleotide variants (SNVs) were found to be likely
CDK12 Cell cycle
ATM Epigenetic oncogenic in the majority of cases
SPOP DNA repair
CDKN1B
CTNNB1 WNT
ZBTB16 MAP kinase • High fraction of oncogenic mutations in AR, TP53,
RNF43
CDKN2A 0 10 20 30 40 50 60 PIK3CA, BRCA2, PTEN, APC, and CDK12
PIK3R1 Alteration frequency
KMT2A
KDM6A
PIK3CB • Mutations in ATM were predicted to be likely oncogenic
FANCA
BRAF in nearly 60%
BRCA1 Mutation
AKT1 Deep deletion
KRAS Amplification
HRAS Fusion

AR, androgen receptor; DDR, DNA damage response; Mcrpc, metastatic castration-resistant prostate cancer; PI3K, phosphoinositide 3-kinase; WNT, wingless integration
Abida W et al. PNAS 2019;116:11428-36.