Abstract 124P
Background
Prostate cancer is a heterogeneous and prevalent disease. We need to know in greater depth the molecular biology of this type of tumors in order to develop new drugs that improve survival in our patients as well as to know who will benefit most from existing treatments. The objective of our abstract is to describe the design, workflow and start-up of the collaborative CAPPRICE project: “Clinical and molecular characterization study of Advanced Prostate Cancer patients in la Princesa University Hospital”.
Methods
The CAPPRICE project is an observational, retrospective, cohort database study, aimed to describe the profile and proportion of germline and/or somatic mutations across the genome, using a customized DDR panel to study key genes (Table), in patients with metastatic castration resistant prostate cancer (mCRPC). Clinical management and outcomes data from patients with available tissue samples and analysed gene mutation status with whole exome or targeted sequencing will be analysed in this study in three timeline cohorts: mCRPC, metastatic castration sensitive prostate cancer (mCSPC) and localized prostate cancer (LPC). The study was approved by the local Ethics Committee. Table: 124P
Gene | Gene type |
BRCA2 | DNA HR repair |
BRCA1 | |
PTEN | Cell signaling |
ATM | DNA damage sensor |
CDK12 | DNA repair/Transcription regulation |
MSH2 | Mismatch DNA repair |
MSH6 | |
MLH1 | |
PSM2 | |
PIK3CA | Cell signaling |
PIK3CB | |
AKT1 | |
PALB2 | DNA HR repair |
BARD1 | |
RAD54L | |
FANCL | |
RAD51D | |
RAD51B | |
CHEK2 | DNA repair |
BRIP1 | DNA HR repair |
FANCA | |
NBN | |
RAD51C | |
CHEK1 | DNA repair |
AR | Androgen signaling |
TP53 | Apoptosis |
MYC | Cell cycle |
RB1 | |
HDAC2 | epigenetic/DNA repair |
APC | Wnt pathway |
CTNNB1 | |
PIK3R1 | Cell Signaling |
EZH2 | Epigenetic/NE PCa |
AURKA | Cell cycle |
MYCN | Cell plasticity/NE PCa |
IDH1 | Mitochondrial metabolism |
IDH2 | |
KMT2D | Epigenetic chromatin reg |
CHD1 | Transcriptional regulation |
HOXB13 | Transcription factor |
SPOP | Taxonomic/Ubiquitin |
Results
We first established a functional working group among the research departments (urology, medical oncology, radiation oncology and pathology) responsible for the coordination, database elaboration, and patients screening. The pathological samples were reviewed to ensure the necessary sample to perform the analysis. In cases without enough tissue, a blood sample from living patients was extracted with prior informed consent to perform germline analysis. A total of 136 patients have met the inclusion criteria and the genetic analysis is currently being carried out. Finally, an outcome analysis plan was designed throughout the mCRPC, mCSPC and LPC cohorts, including only variables and outcomes relevant for that particular cohort.
Conclusions
Teamwork in a multidisciplinary approach is essential for an efficient and comprehensive translational evaluation in prostate cancer research and better understanding the prognosis and treatment of PC patients.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.